> ## Documentation Index > Fetch the complete documentation index at: https://docs.scite.ai/llms.txt > Use this file to discover all available pages before exploring further. # Get Result > Retrieve reference check job status. This allows both fetching the job result and polling for job completion. Whilst the job is in progress its status will be either `PENDING` or `STARTED`. Once the job is complete its status will be `SUCCESS` and the result can be read under the `result` key of this response. ## OpenAPI ````yaml /openapi.json get /reference_check/tasks/{task_id} openapi: 3.1.0 info: title: Scite API description: >- The Scite API provides publication metadata, Smart Citation tallies, citation graphs, literature search, paper recommendations, collections, Reference Check, Assistant, Evidence datasets, and MCP access. Use the **Documentation** tab for task-oriented guides and the **API Reference** tab for endpoint schemas and parameters. ## Authentication Papers and Tallies endpoints are public. Most other endpoints require a bearer credential: ``` Authorization: Bearer ``` Pro users can create and manage keys in the [API Console](https://scite.ai/users/me/api). Available scopes depend on the account. Enterprise credentials, higher limits, and additional scopes are available through [sales](https://scite.ai/contact). See **Authentication** in the Documentation tab for the access matrix, and **Errors and rate limits** for recovery guidance. Use of the API is subject to the [Scite Terms of Use](https://scite.ai/terms). version: latest x-logo: url: https://cdn.scite.ai/assets/images/logo-blue.svg license: name: Scite Terms of Use url: https://scite.ai/terms servers: - url: https://api.scite.ai description: Production security: - BearerAuth: [] tags: - name: Search description: >- Search metadata and citation statements in Scite. Using the Search API for commercial or research use requires a separate license agreement not covered by individual plans. Please email sales@scite.ai for more information. - name: Paper recommendations description: >- Return papers related to a supplied DOI. Recommendations are available for evaluation with eligible Pro access; commercial or research use requires a separate license agreement. Contact sales@scite.ai for licensing. - name: Papers description: >- Retrieve publication metadata by DOI or PMID, including title, abstract, authors, journal, identifiers, retraction status, and editorial notices. Papers endpoints are public. - name: Tallies description: >- Retrieve Smart Citation tallies by DOI. Tally counts represent citation statements; `citingPublications` represents distinct citing publications. Tallies endpoints are public. - name: Smart Citation Graph description: >- Retrieve citations at the in-text level between and from papers by DOI. For example, given a DOI, get a list of citing DOIs including the section and classification of each citation statement. Snippets are not included in the response. Note that these endpoints are restricted without an API token. - name: References description: |- Retrieve references to and from publications by DOI. Note that these endpoints require an API token for usage. - name: Journal description: |- Retrieve aggregate information about journals by ISSN. ### ISSN Format ### A valid ISSN is in the format `dddd-dddC`, where: ``` - d = any decimal digit (0-9) - C = checksum (0-9 or X) ``` - name: Authors description: Retrieve author metadata and papers by author slug. - name: Collections description: >- Create, retrieve, update, and remove collections: sets of papers monitored over time. A dashboard is a report on a collection. - name: Reference Check description: >- Schedule and retrieve reference check jobs. Note that a paid license is required for this feature (please email sales@scite.ai for more information). For an example output report: [see here](https://scite.ai/reference-check/683e0cbc-b322-4692-be6d-f5432b4a453c). - name: Assistant description: >- Ask research questions and receive answers grounded in Scite citation evidence. The Assistant API is asynchronous: 1. Submit a request with `POST /api_partner/assistant/poll` to receive a task ID. 2. Poll `GET /api_partner/assistant/tasks/{task_id}` until the task completes. Both endpoints require a bearer credential with the `assistant` scope. - name: Evidence description: >- Search patents, clinical trials, and grants via the Resolute evidence datasets. Requires an API token with a per-dataset scope (`evidence:patents:api`, `evidence:grants:api`, `evidence:clinical-trials:api`). Please email sales@scite.ai for access. ## Query parameters ### `q` — free-text query Supports boolean operators (`AND`, `OR`, `NOT`) and phrase matching with double quotes. Examples: `q=CRISPR`, `q="gene therapy" AND cancer`, `q=diabetes NOT type+1` ### `f` — field filters Space-delimited filters in `field:"value"` format. **Values must be quoted** with double quotes. Call `GET /schema` for the full list of filterable fields per dataset. **Patent filters**: `patents.filingStatus` (`"application"`, `"grant"`), `patents.assignees.name`, `patents.inventors.name`, `patents.languages` (ISO 639-1, e.g. `"en"`) **Clinical trial filters**: `trialState.phase` (`"Phase I"` .. `"Phase IV"`, `"N/A"`), `trialState.overallStatus` (`"Recruiting"`, `"Completed"`, …), `conditions`, `interventions.name`, `sponsors.name`, `registry` (`"ClinicalTrials.gov"`, `"UMIN-CTR"`, …), `design.studyType` (`"Interventional"`, `"Observational"`) **Grant filters**: `agency`, `organization`, `piName`, `country` (ISO 3166-1 alpha-3, e.g. `"USA"`, `"GBR"`), `dataSource` (`"NIH RePORTER"`, `"NSF"`, …) Example: `f=trialState.phase:"Phase III" trialState.overallStatus:"Recruiting"` **Date range filters** use `gte` (>=) and `lt` (<) suffixes with ISO dates or epoch milliseconds: `f=dates.startDategte:"2024-01-01" dates.startDatelt:"2025-01-01"`. Epoch ms: `f=dates.startDategte:"1704067200000" dates.startDatelt:"1735689600000"`. Dates without a timezone are interpreted as UTC. Timezone offsets are supported: `"2024-01-01T00:00:00+05:00"`. No space between the field name and the suffix. ### `s` — sort mode Default is `_relevance`. Call `GET /schema` to discover sortable fields per dataset. ## Response format note Some fields in search and detail responses may be either a plain string or an object `{"id": "...", "name": "..."}` (and optionally `"highlighted": "..."`), depending on the query. Consumers should handle both shapes, e.g. `value.id ?? value.name ?? value`. - name: PubMed Source Tallies description: >- Retrieve tallies indicating how many times a given paper was cited by documents of various types from PubMed (e.g. how many times was a given DOI cited by practice guidelines). paths: /reference_check/tasks/{task_id}: get: tags: - Reference Check summary: Get Result description: |- Retrieve reference check job status. This allows both fetching the job result and polling for job completion. Whilst the job is in progress its status will be either `PENDING` or `STARTED`. Once the job is complete its status will be `SUCCESS` and the result can be read under the `result` key of this response. operationId: getReferenceCheckResult parameters: - name: task_id in: path required: true schema: type: string title: Task Id - name: authorization in: header required: false schema: type: string description: Set to `Bearer ` to pass token for authorization. title: Authorization description: Set to `Bearer ` to pass token for authorization. responses: '200': description: Successful Response content: application/json: schema: $ref: '#/components/schemas/TaskResponse' '401': $ref: '#/components/responses/Unauthorized' '403': $ref: '#/components/responses/Forbidden' '404': $ref: '#/components/responses/NotFound' '422': description: Validation Error content: application/json: schema: $ref: '#/components/schemas/HTTPValidationError' '429': $ref: '#/components/responses/TooManyRequests' '500': $ref: '#/components/responses/InternalServerError' components: schemas: TaskResponse: properties: status: type: string enum: - PENDING - STARTED - FAILURE - REVOKED - SUCCESS - CANCELLED title: Status overallTally: anyOf: - $ref: '#/components/schemas/TallyResponse' - type: 'null' info: anyOf: - $ref: '#/components/schemas/TaskInfo' - type: 'null' result: anyOf: - $ref: '#/components/schemas/KalaParserReport' - additionalProperties: true type: object - type: 'null' title: Result error: anyOf: - type: string - type: 'null' title: Error papers: anyOf: - additionalProperties: $ref: '#/components/schemas/PaperResponse' type: object - type: 'null' title: Papers tallies: anyOf: - additionalProperties: $ref: '#/components/schemas/TallyResponse' type: object - type: 'null' title: Tallies type: object required: - status title: TaskResponse example: overallTally: contradicting: 98 mentioning: 49577 supporting: 1027 total: 51417 unclassified: 715 papers: 10.1002/hep.26015: abstract: >- Sphingolipids are important structural components of cell membranes and act as critical regulators of cell function by modulating intracellular signaling pathways. Specific sphingolipids, such as ceramide, glucosylceramide, and ganglioside GM3, have been implicated in various aspects of insulin resistance, because they have been shown to modify several steps in the insulin signaling pathway, such as phosphorylation of either protein kinase B (Akt) or of the insulin receptor. We now explore the role of the ceramide acyl chain length in insulin signaling by using a ceramide synthase 2 (CerS2) null mouse, which is unable to synthesize very long acyl chain (C22-C24) ceramides. CerS2 null mice exhibited glucose intolerance despite normal insulin secretion from the pancreas. Both insulin receptor and Akt phosphorylation were abrogated in liver, but not in adipose tissue or in skeletal muscle. The lack of insulin receptor phosphorylation in liver correlated with its inability to translocate into detergent-resistant membranes (DRMs). Moreover, DRMs in CerS2 null mice displayed properties significantly different from those in wild-type mice, suggesting that the altered sphingolipid acyl chain length directly affects insulin receptor translocation and subsequent signaling. Conclusion: We conclude that the sphingolipid acyl chain composition of liver regulates insulin signaling by modifying insulin receptor translocation into membrane microdomains. (HEPATOLOGY 2013;57:525-532) authors: - affiliation: Weizmann Institute of Science affiliationID: '11815' affiliationSlug: weizmann-institute-of-science-b3jp authorID: '178208965' authorName: Joo Won Park authorSequenceNumber: 1 authorSlug: joo-won-park-8GVygVM family: Park given: Joo Won - affiliation: Weizmann Institute of Science affiliationID: '11815' affiliationSlug: weizmann-institute-of-science-b3jp authorID: '13634490' authorName: Woo Jae Park authorSequenceNumber: 2 authorSlug: woo-jae-park-9DXbrG family: Park given: Woo Jae - affiliation: Weizmann Institute of Science affiliationID: '11815' affiliationSlug: weizmann-institute-of-science-b3jp authorID: '11463805' authorName: Yael Kuperman authorSequenceNumber: 3 authorSlug: yael-kuperman-AGNLa3 family: Kuperman given: Yael - affiliation: Weizmann Institute of Science affiliationID: '11815' affiliationSlug: weizmann-institute-of-science-b3jp authorID: '187026' authorName: Sigalit Boura-Halfon authorSequenceNumber: 4 authorSlug: sigalit-boura-halfon-R5099 family: Boura-Halfon given: Sigalit - affiliation: Weizmann Institute of Science affiliationID: '11815' affiliationSlug: weizmann-institute-of-science-b3jp authorID: '6235045' authorName: Yael Pewzner-Jung authorSequenceNumber: 5 authorSlug: yael-pewzner-jung-PQRaLL family: Pewzner-Jung given: Yael - affiliation: Weizmann Institute of Science affiliationID: '11815' affiliationSlug: weizmann-institute-of-science-b3jp authorID: '517393' authorName: Anthony H. Futerman authorSequenceNumber: 6 authorSlug: anthony-h-futerman-ARGJv family: Futerman given: Anthony H. doi: 10.1002/hep.26015 editorialNotices: [] id: 50524713 issns: - 0270-9139 issue: '2' journal: Hepatology journalSlug: 5GEpG keywords: - Steatohepatitis/Metabolic Liver Disease memberId: 311 normalizedTypes: - article page: 525-532 preprintLinks: [] publicationLinks: [] publisher: Wiley retracted: false shortJournal: Hepatology slug: ablation-of-very-long-acyl-GA16lb title: >- Ablation of very long acyl chain sphingolipids causes hepatic insulin resistance in mice due to altered detergent-resistant membranes type: journal-article volume: '57' year: 2012 10.1002/ijc.21422: abstract: >- Monocytes are recruited into tumors from the circulation along defined chemotactic gradients and they then differentiate into tumor-associated macrophages (TAMs). Recent evidence has shown that large numbers of TAMs are attracted to and retained in avascular and necrotic areas, where they are exposed to tumor hypoxia. At these sites, TAMs appear to undergo marked phenotypic changes with activation of hypoxia-inducible transcription factors, dramatically upregulating the expression of a large number of genes encoding mitogenic, proangiogenic and prometastatic cytokines and enzymes. As a consequence, high TAMs density has been correlated with increased tumor growth and angiogenesis in various tumor types. Since hypoxia is a hallmark feature of malignant tumors and hypoxic tumor cells are relatively resistant to radio-and chemotherapy, these areas have become a target for novel forms of anticancer therapy. These include hypoxiatargeted gene therapy in which macrophages are armed with therapeutic genes that are activated by hypoxia-responsive promoter elements. This restricts transgene expression to hypoxic areas, where the gene product is then released and acts on neighboring hypoxic tumor cells or proliferating blood vessels. In this way, the responses of macrophages to tumor hypoxia can be exploited to deliver potent antitumor agents to these poorly vascularized, and thus largely inaccessible, areas of tumors. ' 2005 Wiley-Liss, Inc. authors: - affiliation: University of Sheffield affiliationID: '10452' affiliationSlug: university-of-sheffield-MzKE authorID: '10326446' authorName: Craig Murdoch authorSequenceNumber: 1 authorSlug: craig-murdoch-9bv0Y9 family: Murdoch given: Craig - affiliation: University of Sheffield affiliationID: '10452' affiliationSlug: university-of-sheffield-MzKE authorID: '18992566' authorName: Claire E. Lewis authorSequenceNumber: 2 authorSlug: claire-e-lewis-xPQJVw family: Lewis given: Claire E. doi: 10.1002/ijc.21422 editorialNotices: [] id: 50587440 issns: - 0020-7136 - 1097-0215 issue: '5' journal: International Journal of Cancer journalSlug: ej5Qr keywords: - macrophage - tumor-associated macrophages (TAMs) - angiogenesis - hypoxia - tumor memberId: 311 normalizedTypes: - article page: 701-708 preprintLinks: [] publicationLinks: [] publisher: Wiley retracted: false shortJournal: Int. J. Cancer slug: macrophage-migration-and-gene-expression-L6MNGQ title: >- Macrophage migration and gene expression in response to tumor hypoxia type: journal-article volume: '117' year: 2005 10.1006/bmmb.1993.1059: authors: - affiliation: City Of Hope National Medical Center affiliationID: '1813' affiliationSlug: city-of-hope-national-medical-GbZ authorID: '38973486' authorName: D E Comings authorSequenceNumber: 1 authorSlug: d-e-comings-434RjY family: Comings given: D E - authorID: '238996266' authorName: S.D. Flanagan authorSequenceNumber: 2 authorSlug: s-d-flanagan-xXnzrN3 family: Flanagan given: S.D. - authorID: '27998969' authorName: George Dietz authorSequenceNumber: 3 authorSlug: george-dietz-56lXdZ family: Dietz given: George - authorID: '16332857' authorName: D. Muhleman authorSequenceNumber: 4 authorSlug: d-muhleman-GPYkKA family: Muhleman given: D. - authorID: '12811337' authorName: E. Knell authorSequenceNumber: 5 authorSlug: e-knell-jXPVP5 family: Knell given: E. - authorID: '9120272' authorName: Reinhard Gysin authorSequenceNumber: 6 authorSlug: reinhard-gysin-wbjbdy family: Gysin given: Reinhard doi: 10.1006/bmmb.1993.1059 editorialNotices: [] id: 52091767 issns: - 0885-4505 issue: '2' journal: Biochemical Medicine and Metabolic Biology journalSlug: A38Ya memberId: 78 normalizedTypes: - article page: 176-185 preprintLinks: [] publicationLinks: [] publisher: Elsevier BV retracted: false shortJournal: Biochemical Medicine and Metabolic Biology slug: the-dopamine-d2-receptor-drd2-JMkQkY title: >- The Dopamine D2 Receptor (DRD2) as a Major Gene in Obesity and Height type: journal-article volume: '50' year: 1993 10.1007/s00125-005-1735-1: authors: - affiliation: University of Tokyo affiliationID: '11716' affiliationSlug: university-of-tokyo-QYyz authorID: '8690074' authorName: Nobuhiro Shojima authorSequenceNumber: 1 authorSlug: nobuhiro-shojima-pxjMON family: Shojima given: Nobuhiro - affiliation: Tohoku University affiliationID: '11040' affiliationSlug: tohoku-university-Lz4E authorID: '211303337' authorName: Takehide Ogihara authorSequenceNumber: 2 authorSlug: takehide-ogihara-jMm2nmO family: Ogihara given: Takehide - affiliation: Saitama Medical University affiliationID: '18641' affiliationSlug: saitama-medical-university-XDLA authorID: '8346999' authorName: Kouichi Inukai authorSequenceNumber: 3 authorSlug: kouichi-inukai-ePApMm family: Inukai given: Kouichi - affiliation: University of Tokyo affiliationID: '11716' affiliationSlug: university-of-tokyo-QYyz authorID: '78480766' authorName: Midori Fujishiro authorSequenceNumber: 4 authorSlug: midori-fujishiro-xY4leM family: Fujishiro given: Midori - affiliation: University of Tokyo affiliationID: '11716' affiliationSlug: university-of-tokyo-QYyz authorID: '12700981' authorName: Hideyuki Sakoda authorSequenceNumber: 5 authorSlug: hideyuki-sakoda-jXVgPJ family: Sakoda given: Hideyuki - affiliation: University of Tokyo affiliationID: '11716' affiliationSlug: university-of-tokyo-QYyz authorID: '6124749' authorName: Akifumi Kushiyama authorSequenceNumber: 6 authorSlug: akifumi-kushiyama-A3wbrQ family: Kushiyama given: Akifumi - affiliation: Tohoku University affiliationID: '11040' affiliationSlug: tohoku-university-Lz4E authorID: '80950237' authorName: Hideki Katagiri authorSequenceNumber: 7 authorSlug: hideki-katagiri-jl3d9z family: Katagiri given: Hideki - authorID: '6063891' authorName: Motonobu Anai authorSequenceNumber: 8 authorSlug: motonobu-anai-1ZyzWM family: Anai given: Motonobu - authorID: '29192866' authorName: Hiraku Ono authorSequenceNumber: 9 authorSlug: hiraku-ono-xxMAJw family: Ono given: Hiraku - affiliation: University of Tokyo affiliationID: '11716' affiliationSlug: university-of-tokyo-QYyz authorID: '20980323' authorName: Yasushi Fukushima authorSequenceNumber: 10 authorSlug: yasushi-fukushima-JlrVd0 family: Fukushima given: Yasushi - affiliation: University of Tokyo affiliationID: '11716' affiliationSlug: university-of-tokyo-QYyz authorID: '6301718' authorName: Nanao Horike authorSequenceNumber: 11 authorSlug: nanao-horike-dvEwXj family: Horike given: Nanao - affiliation: University of Tokyo affiliationID: '11716' affiliationSlug: university-of-tokyo-QYyz authorID: '7408258' authorName: Amelia Y.I. Viana authorSequenceNumber: 12 authorSlug: amelia-y-i-viana-gZzzwK family: Viana given: Amelia Y.I. - affiliation: University of Tokyo affiliationID: '11716' affiliationSlug: university-of-tokyo-QYyz authorID: '5464422' authorName: Yasunobu Uchijima authorSequenceNumber: 13 authorSlug: yasunobu-uchijima-xXYWkb family: Uchijima given: Yasunobu - affiliation: University of Tokyo affiliationID: '11716' affiliationSlug: university-of-tokyo-QYyz authorID: '16077383' authorName: Hiroki Kurihara authorSequenceNumber: 14 authorSlug: hiroki-kurihara-a82d9j family: Kurihara given: Hiroki - affiliation: University of Tokyo affiliationID: '11716' affiliationSlug: university-of-tokyo-QYyz authorID: '15656692' authorName: Tomoichiro Asano authorSequenceNumber: 15 authorSlug: tomoichiro-asano-WnKyEw family: Asano given: Tomoichiro doi: 10.1007/s00125-005-1735-1 editorialNotices: [] id: 59412464 issns: - 0012-186X - 1432-0428 issue: '5' journal: Diabetologia journalSlug: PQL9g memberId: 297 normalizedTypes: - article page: 984-992 preprintLinks: [] publicationLinks: [] publisher: Springer Science and Business Media LLC retracted: false shortJournal: Diabetologia slug: serum-concentrations-of-resistin-like-molecules-y5KM3l title: >- Serum concentrations of resistin-like molecules β and γ are elevated in high-fat-fed and obese db/db mice, with increased production in the intestinal tract and bone marrow type: journal-article volume: '48' year: 2005 10.1007/s00125-013-2846-8: abstract: >- Aims/hypothesis Metabolic disorders are commonly investigated using knockout and transgenic mouse models. A variety of mouse strains have been used for this purpose. However, mouse strains can differ in their inherent propensities to develop metabolic disease, which may affect the experimental outcomes of metabolic studies. We have investigated straindependent differences in the susceptibility to diet-induced obesity and insulin resistance in five commonly used inbred mouse strains (C57BL/6J, 129X1/SvJ, BALB/c, DBA/2 and FVB/N). Methods Mice were fed either a low-fat or a high-fat diet (HFD) for 8 weeks. Whole-body energy expenditure and body composition were then determined. Tissues were used to measure markers of mitochondrial metabolism, inflammation, oxidative stress and lipid accumulation. Results BL6, 129X1, DBA/2 and FVB/N mice were all susceptible to varying degrees to HFD-induced obesity, glucose intolerance and insulin resistance, but BALB/c mice exhibited some protection from these detrimental effects. This protection could not be explained by differences in mitochondrial metabolism or oxidative stress in liver or muscle, or inflammation in adipose tissue. Interestingly, in contrast with the other strains, BALB/c mice did not accumulate excess lipid (triacylglycerols and diacylglycerols) in the liver; this is potentially related to lower fatty acid uptake rather than differences in lipogenesis or lipid oxidation. Conclusions/interpretation Collectively, our findings indicate that most mouse strains develop metabolic defects on an HFD. However, there are inherent differences between strains, and thus the genetic background needs to be considered carefully in metabolic studies. Keywords authors: - affiliation: Garvan Institute of Medical Research affiliationID: '18807' affiliationSlug: garvan-institute-of-medical-research-Y0EG authorID: '18166098' authorName: Magdalene K. Montgomery authorSequenceNumber: 1 authorSlug: magdalene-k-montgomery-6JAODr family: Montgomery given: Magdalene K. - affiliation: Garvan Institute of Medical Research affiliationID: '18807' affiliationSlug: garvan-institute-of-medical-research-Y0EG authorID: '97047997' authorName: Nicole L Hallahan authorSequenceNumber: 2 authorSlug: nicole-l-hallahan-vvrjdV family: Hallahan given: Nicole L - affiliation: University of Wollongong affiliationID: '20782' affiliationSlug: university-of-wollongong-VWYO authorID: '17560038' authorName: Simon H. J. Brown authorSequenceNumber: 3 authorSlug: simon-h-j-brown-VyPjvM family: Brown given: Simon H. J. - affiliation: Garvan Institute of Medical Research affiliationID: '18807' affiliationSlug: garvan-institute-of-medical-research-Y0EG authorID: '52122459' authorName: Menghan Liu authorSequenceNumber: 4 authorSlug: menghan-liu-bnvKEW family: Liu given: Menghan - affiliation: University of Wollongong affiliationID: '20782' affiliationSlug: university-of-wollongong-VWYO authorID: '18720972' authorName: Todd W. Mitchell authorSequenceNumber: 5 authorSlug: todd-w-mitchell-wVJAyr family: Mitchell given: Todd W. - affiliation: Garvan Institute of Medical Research affiliationID: '18807' affiliationSlug: garvan-institute-of-medical-research-Y0EG authorID: '8713947' authorName: Gregory J. Cooney authorSequenceNumber: 6 authorSlug: gregory-j-cooney-1gxvRX family: Cooney given: Gregory J. - affiliation: Garvan Institute of Medical Research affiliationID: '18807' affiliationSlug: garvan-institute-of-medical-research-Y0EG authorID: '66870151' authorName: Nigel Turner authorSequenceNumber: 7 authorSlug: nigel-turner-Yk1yJK family: Turner given: Nigel doi: 10.1007/s00125-013-2846-8 editorialNotices: [] id: 59415386 issns: - 0012-186X - 1432-0428 issue: '5' journal: Diabetologia journalSlug: PQL9g memberId: 297 normalizedTypes: - article page: 1129-1139 preprintLinks: [] publicationLinks: [] publisher: Springer Science and Business Media LLC retracted: false shortJournal: Diabetologia slug: mouse-strain-dependent-variation-in-obesity-4X12WV title: >- Mouse strain-dependent variation in obesity and glucose homeostasis in response to high-fat feeding type: journal-article volume: '56' year: 2013 10.1007/s11892-008-0032-z: abstract: >- Ectopic fat is defined by the deposition of triglycerides within cells of non-adipose tissue that normally contain only small amounts of fat. Over the past decade, magnetic resonance spectroscopy has been used extensively for noninvasive quantification of intramyocellular, intrahepatocellular, and more recently myocardial and pancreatic lipids. In liver and muscle, triglyceride content usually correlates with whole-body and tissue-specific insulin sensitivity. However, fat mass and oxidative capacity influence this relationship, indicating that ectopic lipid content is not the only factor that explains insulin resistance. Ectopic lipids may rather serve as biomarkers of the balance between metabolic supply and demand in different states of insulin sensitivity. Consequently, ectopic lipid concentrations, particularly in the liver, decrease with lifestyle- or drug-induced improvement of insulin sensitivity. authors: - affiliation: Hanusch Hospital affiliationID: '197271' affiliationSlug: hanusch-hospital-NM0w9 authorID: '11468441' authorName: Angelika Lettner authorSequenceNumber: 1 authorSlug: angelika-lettner-X4eL6k family: Lettner given: Angelika - affiliation: Hanusch Hospital affiliationID: '197271' affiliationSlug: hanusch-hospital-NM0w9 authorID: '144668417' authorName: Michael Roden authorSequenceNumber: 2 authorSlug: michael-roden-Ezr13L family: Roden given: Michael doi: 10.1007/s11892-008-0032-z editorialNotices: [] id: 61188900 issns: - 1534-4827 - 1539-0829 issue: '3' journal: Current Diabetes Reports journalSlug: jMJGJ memberId: 297 normalizedTypes: - article page: 185-191 preprintLinks: [] publicationLinks: [] publisher: Springer Science and Business Media LLC retracted: false shortJournal: Curr Diab Rep slug: ectopic-fat-and-insulin-resistance-3g5eOO title: Ectopic fat and insulin resistance type: journal-article volume: '8' year: 2008 10.1016/j.cell.2012.02.017: abstract: >- Insulin resistance is a complex metabolic disorder that defies a single etiological pathway. Accumulation of ectopic lipid metabolites, activation of the unfolded protein response (UPR) pathway and innate immune pathways have all been implicated in the pathogenesis of insulin resistance. However, these pathways are also closely linked to changes in fatty acid uptake, lipogenesis, and energy expenditure that can impact ectopic lipid deposition. Ultimately, accumulation of specific lipid metabolites (diacylglycerols and/or ceramides) in liver and skeletal muscle, may be a common pathway leading to impaired insulin signaling and insulin resistance. authors: - affiliation: Yale University affiliationID: '8068' affiliationSlug: yale-university-kyQE authorID: '10373696' authorName: Varman T. Samuel authorSequenceNumber: 1 authorSlug: varman-t-samuel-M2rnek family: Samuel given: Varman T. - affiliation: Yale University affiliationID: '8068' affiliationSlug: yale-university-kyQE authorID: '5886223' authorName: Gerald I. Shulman authorSequenceNumber: 2 authorSlug: gerald-i-shulman-J1LvKY family: Shulman given: Gerald I. doi: 10.1016/j.cell.2012.02.017 editorialNotices: [] id: 67157549 issns: - 0092-8674 issue: '5' journal: Cell journalSlug: pnm4z keywords: - Article memberId: 78 normalizedTypes: - article page: 852-871 preprintLinks: [] publicationLinks: [] publisher: Elsevier BV retracted: false shortJournal: Cell slug: mechanisms-for-insulin-resistance-common-Aazynv title: >- Mechanisms for Insulin Resistance: Common Threads and Missing Links type: journal-article volume: '148' year: 2012 10.1016/j.cell.2014.03.066: abstract: >- SUMMARY Beige fat, which expresses the thermogenic protein UCP1, provides a defense against cold and obesity. Although a cold environment is the physiologic stimulus for inducing beige fat in mice and humans, the events that lead from the sensing of cold to the development of beige fat remain poorly understood. Here, we identify the efferent beige fat thermogenic circuit, consisting of eosinophils, type 2 cytokines interleukin (IL)-4/13 and alternatively activated macrophages. Genetic loss of eosinophils or IL-4/13 signaling impairs cold-induced biogenesis of beige fat. Mechanistically, macrophages recruited to cold-stressed subcutaneous white adipose tissue (scWAT) undergo alternative activation to induce tyrosine hydroxylase expression and catecholamine production, factors required for browning of scWAT. Conversely, administration of IL-4 to thermoneutral mice increases beige fat mass and thermogenic capacity to ameliorate pre-established obesity. Together, our findings have uncovered the efferent circuit controlling biogenesis of beige fat and provide support for its targeting to treat obesity. authors: - affiliation: University of California, San Francisco affiliationID: '12272' affiliationSlug: university-of-california-san-francisco-w1Ry authorID: '32615577' authorName: Yifu Qiu authorSequenceNumber: 1 authorSlug: yifu-qiu-n15v8D family: Qiu given: Yifu - affiliation: University of California, San Francisco affiliationID: '12272' affiliationSlug: university-of-california-san-francisco-w1Ry authorID: '19867627' authorName: Khoa D. Nguyen authorSequenceNumber: 2 authorSlug: khoa-d-nguyen-N802GN family: Nguyen given: Khoa D. - affiliation: University of California, San Francisco affiliationID: '12272' affiliationSlug: university-of-california-san-francisco-w1Ry authorID: '5895306' authorName: Justin I. Odegaard authorSequenceNumber: 3 authorSlug: justin-i-odegaard-zRGZz3 family: Odegaard given: Justin I. - affiliation: University of California, San Francisco affiliationID: '12272' affiliationSlug: university-of-california-san-francisco-w1Ry authorID: '81078612' authorName: Xiaojin Cui authorSequenceNumber: 4 authorSlug: xiaojin-cui-02DQmP family: Cui given: Xiaojin - affiliation: University of California, San Francisco affiliationID: '12272' affiliationSlug: university-of-california-san-francisco-w1Ry authorID: '15221801' authorName: Xiao Yu Tian authorSequenceNumber: 5 authorSlug: xiao-yu-tian-Pvz4rQ family: Tian given: Xiao Yu - affiliation: University of California, San Francisco affiliationID: '12272' affiliationSlug: university-of-california-san-francisco-w1Ry authorID: '6048470' authorName: Richard M. Locksley authorSequenceNumber: 6 authorSlug: richard-m-locksley-RVle83 family: Locksley given: Richard M. - affiliation: University of Washington affiliationID: '11969' affiliationSlug: university-of-washington-5JeG authorID: '398890' authorName: Richard D. Palmiter authorSequenceNumber: 7 authorSlug: richard-d-palmiter-9g4O4 family: Palmiter given: Richard D. - affiliation: University of California, San Francisco affiliationID: '12272' affiliationSlug: university-of-california-san-francisco-w1Ry authorID: '32477922' authorName: Ajay Chawla authorSequenceNumber: 8 authorSlug: ajay-chawla-xpjLMg family: Chawla given: Ajay doi: 10.1016/j.cell.2014.03.066 editorialNotices: [] id: 67158910 issns: - 0092-8674 issue: '6' journal: Cell journalSlug: pnm4z keywords: - Article memberId: 78 normalizedTypes: - article page: 1292-1308 preprintLinks: [] publicationLinks: [] publisher: Elsevier BV retracted: false shortJournal: Cell slug: eosinophils-and-type-2-cytokine-64K4kr title: >- Eosinophils and Type 2 Cytokine Signaling in Macrophages Orchestrate Development of Functional Beige Fat type: journal-article volume: '157' year: 2014 10.1016/j.celrep.2016.06.007: abstract: >- Summary Clostridium difficile infection (CDI) is the most common cause of hospital-acquired infection in the United States. Host susceptibility and the severity of infection are influenced by disruption of the microbiota and the immune response. However, how the microbiota regulates immune responses to mediate CDI outcome remains unclear. Here, we investigated the role of the microbiota-linked cytokine IL-25 during infection. Intestinal IL-25 was suppressed during CDI in humans and mice. Restoration of IL-25 reduced CDI-associated mortality and tissue pathology even though equivalent levels of C. difficile bacteria and toxin remained in the gut. IL-25 protection was mediated by gut eosinophils, as demonstrated by an increase in intestinal eosinophils and a loss of IL-25 protection upon eosinophil depletion. These findings support a mechanism whereby the induction of IL-25-mediated eosinophilia can reduce host mortality during active CDI. This work may provide targets for future development of microbial or immune-based therapies. authors: - affiliation: University of Virginia affiliationID: '26257' affiliationSlug: university-of-virginia-GAeJ authorID: '9988090' authorName: Erica L. Buonomo authorSequenceNumber: 1 authorSlug: erica-l-buonomo-9b1pNb family: Buonomo given: Erica L. - affiliation: University of Virginia affiliationID: '26257' affiliationSlug: university-of-virginia-GAeJ authorID: '4017735' authorName: Carrie A. Cowardin authorSequenceNumber: 2 authorSlug: carrie-a-cowardin-K6lp3p family: Cowardin given: Carrie A. - affiliation: University of Virginia affiliationID: '26257' affiliationSlug: university-of-virginia-GAeJ authorID: '24766195' authorName: Madeline G. Wilson authorSequenceNumber: 3 authorSlug: madeline-g-wilson-Yjv6QD family: Wilson given: Madeline G. - affiliation: University of Virginia affiliationID: '26257' affiliationSlug: university-of-virginia-GAeJ authorID: '67903236' authorName: Mahmoud M. Saleh authorSequenceNumber: 4 authorSlug: mahmoud-m-saleh-l166PE family: Saleh given: Mahmoud M. - affiliation: University of Virginia affiliationID: '26257' affiliationSlug: university-of-virginia-GAeJ authorID: '6063859' authorName: Patcharin Pramoonjago authorSequenceNumber: 5 authorSlug: patcharin-pramoonjago-b2rY3k family: Pramoonjago given: Patcharin - affiliation: University of Virginia affiliationID: '26257' affiliationSlug: university-of-virginia-GAeJ authorID: '21744467' authorName: William A. Petri authorSequenceNumber: 6 authorSlug: william-a-petri-JlYGXE family: Petri given: William A. doi: 10.1016/j.celrep.2016.06.007 editorialNotices: [] id: 67169759 issns: - 2211-1247 issue: '2' journal: Cell Reports journalSlug: b2DYr keywords: - Article memberId: 78 normalizedTypes: - article page: 432-443 preprintLinks: [] publicationLinks: [] publisher: Elsevier BV retracted: false shortJournal: Cell Reports slug: microbiota-regulated-il-25-increases-eosinophil-number-bmapM1 title: >- Microbiota-Regulated IL-25 Increases Eosinophil Number to Provide Protection during Clostridium difficile Infection type: journal-article volume: '16' year: 2016 10.1016/j.molmet.2017.12.004: abstract: >- ObjectiveObesity is a metabolic disorder that has reached epidemic proportions worldwide and leads to increased risk for diabetes, cardiovascular disease, asthma, certain cancers, and various other diseases. Obesity and its comorbidities are associated with impaired adipose tissue (AT) function. In the last decade, eosinophils have been identified as regulators of proper AT function. Our study aimed to determine whether normalizing the number of AT eosinophils in obese mice, to those of lean healthy mice, would reduce obesity and/or improve metabolic fitness.MethodsC57BL/6J mice fed a high fat diet (HFD) were simultaneously given recombinant interleukin-5 (rIL5) for 8 weeks to increase AT eosinophils. Metabolic fitness was tested by evaluating weight gain, AT inflammation, glucose, lipid, and mixed-meal tolerance, AT insulin signaling, energy substrate utilization, energy expenditure, and white AT beiging capacity.ResultsEosinophils were increased ∼3-fold in AT of obese HFD-fed mice treated with rIL5, and thus were restored to levels observed in lean healthy mice. However, there were no significant differences in rIL5-treated mice among the above listed comprehensive set of metabolic assays, despite the increased AT eosinophils.ConclusionsWe have shown that restoring obese AT eosinophils to lean healthy levels is not sufficient to allow for improvement in any of a range of metabolic features otherwise impaired in obesity. Thus, the mechanisms that identified eosinophils as positive regulators of AT function, and therefore systemic health, are more complex than initially understood and will require further study to fully elucidate. authors: - affiliation: Vanderbilt University affiliationID: '16364' affiliationSlug: vanderbilt-university-ypnx authorID: '11125700' authorName: W. Reid Bolus authorSequenceNumber: 1 authorSlug: w-reid-bolus-38VwWO family: Bolus given: W. Reid - affiliation: Vanderbilt University affiliationID: '16364' affiliationSlug: vanderbilt-university-ypnx authorID: '56697354' authorName: Kristin R. Peterson authorSequenceNumber: 2 authorSlug: kristin-r-peterson-6jwyP9 family: Peterson given: Kristin R. - affiliation: Vanderbilt University affiliationID: '16364' affiliationSlug: vanderbilt-university-ypnx authorID: '8524948' authorName: Merla J. Hubler authorSequenceNumber: 3 authorSlug: merla-j-hubler-WGdxJO family: Hubler given: Merla J. - affiliation: Vanderbilt University affiliationID: '16364' affiliationSlug: vanderbilt-university-ypnx authorID: '21870360' authorName: Arion Kennedy authorSequenceNumber: 4 authorSlug: arion-kennedy-Qkw9NX family: Kennedy given: Arion - affiliation: Vanderbilt University affiliationID: '16364' affiliationSlug: vanderbilt-university-ypnx authorID: '67455575' authorName: Marnie L. Gruen authorSequenceNumber: 5 authorSlug: marnie-l-gruen-ZkMNv9 family: Gruen given: Marnie L. - affiliation: Vanderbilt University affiliationID: '16364' affiliationSlug: vanderbilt-university-ypnx authorID: '3944334' authorName: Alyssa H. Hasty authorSequenceNumber: 6 authorSlug: alyssa-h-hasty-OVjb2k family: Hasty given: Alyssa H. doi: 10.1016/j.molmet.2017.12.004 editorialNotices: [] id: 242253400 issns: - 2212-8778 journal: Molecular Metabolism journalSlug: lZrJ3 keywords: - Original Article memberId: 78 normalizedTypes: - article page: 86-95 preprintLinks: [] publicationLinks: [] publisher: Elsevier BV retracted: false shortJournal: Molecular Metabolism slug: elevating-adipose-eosinophils-in-obese-3ndxRPK title: >- Elevating adipose eosinophils in obese mice to physiologically normal levels does not rescue metabolic impairments type: journal-article volume: '8' year: 2018 10.1038/ijo.2008.229: abstract: >- Recent studies consistently support a hypoxia response in the adipose tissue in obese animals. The observations have led to the formation of an exciting concept, adipose tissue hypoxia (ATH), in the understanding of major disorders associated with obesity. ATH may provide cellular mechanisms for chronic inflammation, macrophage infiltration, adiponectin reduction, leptin elevation, adipocyte death, endoplasmic reticulum stress and mitochondrial dysfunction in white adipose tissue in obesity. The concept suggests that inhibition of adipogenesis and triglyceride synthesis by hypoxia may be a new mechanism for elevated free fatty acids in the circulation in obesity. ATH may represent a unified cellular mechanism for a variety of metabolic disorders and insulin resistance in patients with metabolic syndrome. It suggests a new mechanism of pathogenesis of insulin resistance and inflammation in obstructive sleep apnea. In addition, it may help us to understand the beneficial effects of caloric restriction, physical exercise and angiotensin II inhibitors in the improvement of insulin sensitivity. In this review article, literatures are reviewed to summarize the evidence and possible cellular mechanisms of ATH. The directions and road blocks in the future studies are analyzed. authors: - affiliation: Pennington Biomedical Research Center affiliationID: '16649' affiliationSlug: pennington-biomedical-research-center-A5ra authorID: '14162755' authorName: Jianping Ye authorSequenceNumber: 1 authorSlug: jianping-ye-e6J2MO family: Ye given: Jianping doi: 10.1038/ijo.2008.229 editorialNotices: [] id: 81259318 issns: - 0307-0565 - 1476-5497 issue: '1' journal: International Journal of Obesity journalSlug: QePv9 keywords: - adipose tissue - insulin resistance - hypoxia - inflammation - angiogenesis memberId: 297 normalizedTypes: - article page: 54-66 preprintLinks: [] publicationLinks: [] publisher: Springer Science and Business Media LLC retracted: false shortJournal: Int J Obes slug: emerging-role-of-adipose-tissue-dlEPxb title: >- Emerging role of adipose tissue hypoxia in obesity and insulin resistance type: journal-article volume: '33' year: 2008 10.1038/mi.2014.123: abstract: >- Eosinophils are multifunctional leukocytes that reside in the gastrointestinal (GI) lamina propria, where their basal function remains largely unexplored. In this study, by examining mice with a selective deficiency of systemic eosinophils (by lineage ablation) or GI eosinophils (eotaxin-1/2 double–deficient or CC chemokine receptor 3–deficient), we show that eosinophils support immunoglobulin A (IgA) class switching, maintain intestinal mucus secretions, affect intestinal microbial composition, and promote the development of Peyer’s patches. Eosinophil-deficient mice showed reduced expression of mediators of secretory IgA production, including intestinal interleukin 1β (IL-1β), inducible nitric oxide synthase, lymphotoxin (LT) α, and LT-β, and reduced levels of retinoic acid-related orphan receptor gamma t–positive (ROR-γt+) innate lymphoid cells (ILCs) while maintaining normal levels of APRIL (a proliferation-inducing ligand), BAFF (B cell–activating factor of the tumor necrosis factor family), and TGF-β (transforming growth factor β). GI eosinophils expressed a relatively high level of IL-1β, and IL-1β–deficient mice manifested the altered gene expression profiles observed in eosinophil-deficient mice and decreased levels of IgA+ cells and ROR-γt+ ILCs. On the basis of these collective data, we propose that eosinophils are required for homeostatic intestinal immune responses including IgA production and that their affect is mediated via IL-1β in the small intestine. authors: - affiliation: Cincinnati Children's Hospital Medical Center affiliationID: '16374' affiliationSlug: cincinnati-children-s-hospital-medical-center-pADQ authorID: '139679076' authorName: Yun-Jae Jung authorSequenceNumber: 1 authorSlug: yun-jae-jung-2PO1JE family: Jung given: Yun-Jae - affiliation: Cincinnati Children's Hospital Medical Center affiliationID: '16374' affiliationSlug: cincinnati-children-s-hospital-medical-center-pADQ authorID: '17384861' authorName: Ting Wen authorSequenceNumber: 2 authorSlug: ting-wen-EOXp5P family: Wen given: Ting - affiliation: University of Cincinnati affiliationID: '19659' affiliationSlug: university-of-cincinnati-bQ3Z authorID: '411647800' authorName: M K Mingler authorSequenceNumber: 3 authorSlug: m-k-mingler-38LOGQO family: Mingler given: M K - affiliation: University of Cincinnati affiliationID: '19659' affiliationSlug: university-of-cincinnati-bQ3Z authorID: '346531809' authorName: J M Caldwell authorSequenceNumber: 4 authorSlug: j-m-caldwell-vydAJ14 family: Caldwell given: J M - affiliation: University of Cincinnati affiliationID: '19659' affiliationSlug: university-of-cincinnati-bQ3Z authorID: '48788791' authorName: Y H Wang authorSequenceNumber: 5 authorSlug: y-h-wang-1vR92W family: Wang given: Y H - affiliation: University of Alabama at Birmingham affiliationID: '26599' affiliationSlug: university-of-alabama-at-birmingham-eNxm authorID: '69032083' authorName: David D. Chaplin authorSequenceNumber: 6 authorSlug: david-d-chaplin-a66kyx family: Chaplin given: David D. - affiliation: Gachon University affiliationID: '9120' affiliationSlug: gachon-university-yJdl authorID: '176464118' authorName: E H Lee authorSequenceNumber: 7 authorSlug: e-h-lee-dvKK5a9 family: Lee given: E H - affiliation: Pohang University of Science and Technology affiliationID: '12801' affiliationSlug: pohang-university-of-science-and-Pl3k authorID: '27638113' authorName: Myoung Ho Jang authorSequenceNumber: 8 authorSlug: myoung-ho-jang-G2ygMb family: Jang given: Myoung Ho - affiliation: Ewha Womans University affiliationID: '20765' affiliationSlug: ewha-womans-university-8Wb3 authorID: '20013547' authorName: So Youn Woo authorSequenceNumber: 9 authorSlug: so-youn-woo-15xObj family: Woo given: So Youn - affiliation: Ewha Womans University affiliationID: '20765' affiliationSlug: ewha-womans-university-8Wb3 authorID: '7285494' authorName: Ju Young Seoh authorSequenceNumber: 10 authorSlug: ju-young-seoh-zR4kwE family: Seoh given: Ju Young - affiliation: Osaka University affiliationID: '2722' affiliationSlug: osaka-university-xX9D authorID: '20136199' authorName: Masayuki Miyasaka authorSequenceNumber: 11 authorSlug: masayuki-miyasaka-enkk90 family: Miyasaka given: Masayuki - affiliation: University of Cincinnati affiliationID: '19659' affiliationSlug: university-of-cincinnati-bQ3Z authorID: '11358116' authorName: Marc E. Rothenberg authorSequenceNumber: 12 authorSlug: marc-e-rothenberg-QmeOgJ family: Rothenberg given: Marc E. doi: 10.1038/mi.2014.123 editorialNotices: [] id: 81304296 issns: - 1933-0219 - 1935-3456 issue: '4' journal: Mucosal Immunology journalSlug: OV5EQ keywords: - Article memberId: 297 normalizedTypes: - article page: 930-942 preprintLinks: [] publicationLinks: [] publisher: Springer Science and Business Media LLC retracted: false shortJournal: Mucosal Immunol slug: il-1-in-eosinophil-mediated-small-intestinal-Mv4WYd title: >- IL-1β in eosinophil-mediated small intestinal homeostasis and IgA production type: journal-article volume: '8' year: 2015 10.1038/nature05483: abstract: >- Adipocytes have been studied with increasing intensity as a result of the emergence of obesity as a serious public health problem and the realization that adipose tissue serves as an integrator of various physiological pathways. In particular, their role in calorie storage makes adipocytes well suited to the regulation of energy balance. Adipose tissue also serves as a crucial integrator of glucose homeostasis. Knowledge of adipocyte biology is therefore crucial for understanding the pathophysiological basis of obesity and metabolic diseases such as type 2 diabetes. Furthermore, the rational manipulation of adipose physiology is a promising avenue for therapy of these conditions. authors: - authorID: '23569687' authorName: Evan D. Rosen authorSequenceNumber: 1 authorSlug: evan-d-rosen-mALkWz family: Rosen given: Evan D. - affiliation: Harvard University affiliationID: '14927' affiliationSlug: harvard-university-NmzP authorID: '376984' authorName: Bruce M. Spiegelman authorSequenceNumber: 2 authorSlug: bruce-m-spiegelman-LAYWm family: Spiegelman given: Bruce M. doi: 10.1038/nature05483 editorialNotices: [] id: 81323364 issns: - 0028-0836 - 1476-4687 issue: '7121' journal: Nature journalSlug: wmGvz keywords: [] memberId: 297 normalizedTypes: - article page: 847-853 preprintLinks: [] publicationLinks: [] publisher: Springer Science and Business Media LLC retracted: false shortJournal: Nature slug: adipocytes-as-regulators-of-energy-ymzOyl title: Adipocytes as regulators of energy balance and glucose homeostasis type: journal-article volume: '444' year: 2006 10.1038/nbt.1621: abstract: >- High-throughput mRNA sequencing (RNA-Seq) holds the promise of simultaneous transcript discovery and abundance estimation1-3. We introduce an algorithm for transcript assembly coupled with a statistical model for RNA-Seq experiments that produces estimates of abundances. Our algorithms are implemented in an open source software program called Cufflinks. To test Cufflinks, we sequenced and analyzed more than 430 million paired 75bp RNA-Seq reads from a mouse myoblast cell line representing a differentiation time series. We detected 13,692 known transcripts and 3,724 previously unannotated ones, 62% of which are supported by independent expression data or by homologous genes in other species. Analysis of transcript expression over the time series revealed complete switches in the dominant transcription start site (TSS) or splice-isoform in 330 genes, along with more subtle shifts in a further 1,304 genes. These dynamics suggest substantial regulatory flexibility and complexity in this well-studied model of muscle development. authors: - affiliation: University of Maryland, College Park affiliationID: '2613' affiliationSlug: university-of-maryland-college-park-G3YK authorID: '8885272' authorName: Cole Trapnell authorSequenceNumber: 1 authorSlug: cole-trapnell-wb9XKL family: Trapnell given: Cole - affiliation: California Institute of Technology affiliationID: '9687' affiliationSlug: california-institute-of-technology-mb8j authorID: '81257310' authorName: Brian A. Williams authorSequenceNumber: 2 authorSlug: brian-a-williams-623WzM family: Williams given: Brian A. - affiliation: University of Maryland, College Park affiliationID: '2613' affiliationSlug: university-of-maryland-college-park-G3YK authorID: '11546170' authorName: Geo Pertea authorSequenceNumber: 3 authorSlug: geo-pertea-RjjyJN family: Pertea given: Geo - affiliation: California Institute of Technology affiliationID: '9687' affiliationSlug: california-institute-of-technology-mb8j authorID: '22304516' authorName: Ali Mortazavi authorSequenceNumber: 4 authorSlug: ali-mortazavi-Qk5wxw family: Mortazavi given: Ali - affiliation: California Institute of Technology affiliationID: '9687' affiliationSlug: california-institute-of-technology-mb8j authorID: '19605467' authorName: Gordon Kwan authorSequenceNumber: 5 authorSlug: gordon-kwan-JlZ3pY family: Kwan given: Gordon - affiliation: Washington University in St. Louis affiliationID: '19037' affiliationSlug: washington-university-in-st-louis-jjaJ authorID: '33888465' authorName: Marijke J. van Baren authorSequenceNumber: 6 authorSlug: marijke-j-van-baren-8OG15a family: Baren given: Marijke J. van - affiliation: University of Maryland, College Park affiliationID: '2613' affiliationSlug: university-of-maryland-college-park-G3YK authorID: '483606902' authorName: Steven L. Salzberg authorSequenceNumber: 7 authorSlug: steven-l-salzberg-9bPOnP9 family: Salzberg given: Steven L. - affiliation: California Institute of Technology affiliationID: '9687' affiliationSlug: california-institute-of-technology-mb8j authorID: '13876604' authorName: Barbara J. Wold authorSequenceNumber: 8 authorSlug: barbara-j-wold-WxmjWJ family: Wold given: Barbara J. - affiliation: University of California, Berkeley affiliationID: '19129' affiliationSlug: university-of-california-berkeley-rDm3 authorID: '8878157' authorName: Lior Pachter authorSequenceNumber: 9 authorSlug: lior-pachter-G5yZdA family: Pachter given: Lior doi: 10.1038/nbt.1621 editorialNotices: [] id: 81334047 issns: - 1087-0156 - 1546-1696 issue: '5' journal: Nature Biotechnology journalSlug: QePXQ keywords: - Article memberId: 297 normalizedTypes: - article page: 511-515 preprintLinks: [] publicationLinks: [] publisher: Springer Science and Business Media LLC retracted: false shortJournal: Nat Biotechnol slug: transcript-assembly-and-quantification-by-14aEdn title: >- Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation type: journal-article volume: '28' year: 2010 10.1038/ncb942: abstract: >- Pluripotent mesenchymal stem cells in bone marrow differentiate into adipocytes, osteoblasts and other cells. Balanced cytodifferentiation of stem cells is essential for the formation and maintenance of bone marrow; however, the mechanisms that control this balance remain largely unknown. Whereas cytokines such as interleukin-1 (IL-1) and tumour-necrosis factor-alpha (TNF-alpha) inhibit adipogenesis, the ligand-induced transcription factor peroxisome proliferator-activated receptor-gamma (PPAR-gamma), is a key inducer of adipogenesis. Therefore, regulatory coupling between cytokine- and PPAR-gamma-mediated signals might occur during adipogenesis. Here we show that the ligand-induced transactivation function of PPAR-gamma is suppressed by IL-1 and TNF-alpha, and that this suppression is mediated through NF-kappaB activated by the TAK1/TAB1/NF-kappaB-inducing kinase (NIK) cascade, a downstream cascade associated with IL-1 and TNF-alpha signalling. Unlike suppression of the PPAR-gamma transactivation function by mitogen-activated protein kinase-induced growth factor signalling through phosphorylation of the A/B domain, NF-kappaB blocks PPAR-gamma binding to DNA by forming a complex with PPAR-gamma and its AF-1-specific co-activator PGC-2. Our results suggest that expression of IL-1 and TNF-alpha in bone marrow may alter the fate of pluripotent mesenchymal stem cells, directing cellular differentiation towards osteoblasts rather than adipocytes by suppressing PPAR-gamma function through NF-kappaB activated by the TAK1/TAB1/NIK cascade. authors: - affiliation: University of Tokyo affiliationID: '11716' affiliationSlug: university-of-tokyo-QYyz authorID: '385146832' authorName: Miyuki Suzawa authorSequenceNumber: 1 authorSlug: miyuki-suzawa-2WX942D family: Suzawa given: Miyuki - affiliation: University of Tokyo affiliationID: '11716' affiliationSlug: university-of-tokyo-QYyz authorID: '10649873' authorName: Ichiro Takada authorSequenceNumber: 2 authorSlug: ichiro-takada-rxwyEA family: Takada given: Ichiro - affiliation: University of Tokyo affiliationID: '11716' affiliationSlug: university-of-tokyo-QYyz authorID: '140018780' authorName: Junn Yanagisawa authorSequenceNumber: 3 authorSlug: junn-yanagisawa-lxgANM family: Yanagisawa given: Junn - affiliation: University of Tokyo affiliationID: '11716' affiliationSlug: university-of-tokyo-QYyz authorID: '7433361' authorName: Fumiaki Ohtake authorSequenceNumber: 4 authorSlug: fumiaki-ohtake-EWvNmW family: Ohtake given: Fumiaki - affiliation: National Institute for Basic Biology affiliationID: '7342' affiliationSlug: national-institute-for-basic-biology-4ZMN authorID: '28753366' authorName: Satoko Ogawa authorSequenceNumber: 5 authorSlug: satoko-ogawa-xxjk4g family: Ogawa given: Satoko - affiliation: University of Tokyo affiliationID: '11716' affiliationSlug: university-of-tokyo-QYyz authorID: '8070377' authorName: Toshimasa Yamauchi authorSequenceNumber: 6 authorSlug: toshimasa-yamauchi-ng0ZPN family: Yamauchi given: Toshimasa - affiliation: University of Tokyo affiliationID: '11716' affiliationSlug: university-of-tokyo-QYyz authorID: '205520820' authorName: Toshimasa Yamauchi authorSequenceNumber: 6 authorSlug: toshimasa-yamauchi-y8waOn6 family: Yamauchi given: Toshimasa - affiliation: University of Tokyo affiliationID: '11716' affiliationSlug: university-of-tokyo-QYyz authorID: '261239592' authorName: Takashi Kadowaki authorSequenceNumber: 7 authorSlug: takashi-kadowaki-W8Lmzyg family: Kadowaki given: Takashi - affiliation: University of Tokyo affiliationID: '11716' affiliationSlug: university-of-tokyo-QYyz authorID: '81359524' authorName: Yasuhiro Takeuchi authorSequenceNumber: 8 authorSlug: yasuhiro-takeuchi-klWy5y family: Takeuchi given: Yasuhiro - affiliation: National Institute for Basic Biology affiliationID: '7342' affiliationSlug: national-institute-for-basic-biology-4ZMN authorID: '76280891' authorName: Hiroshi Shibuya authorSequenceNumber: 9 authorSlug: hiroshi-shibuya-1Qj4Jy family: Shibuya given: Hiroshi - affiliation: University of Tokyo affiliationID: '11716' affiliationSlug: university-of-tokyo-QYyz authorID: '27430905' authorName: Yukiko Gotoh authorSequenceNumber: 10 authorSlug: yukiko-gotoh-ADKWQe family: Gotoh given: Yukiko - affiliation: Nagoya University affiliationID: '8173' affiliationSlug: nagoya-university-rLD3 authorID: '19915519' authorName: Kunihiro Matsumoto authorSequenceNumber: 11 authorSlug: kunihiro-matsumoto-DR9k0e family: Matsumoto given: Kunihiro - affiliation: University of Tokyo affiliationID: '11716' affiliationSlug: university-of-tokyo-QYyz authorID: '144333332' authorName: Shigeaki Kato authorSequenceNumber: 12 authorSlug: shigeaki-kato-25kG4L family: Kato given: Shigeaki doi: 10.1038/ncb942 editorialNotices: - date: '2014-10-31' doi: 10.1038/ncb942 noticeDoi: 10.1038/ncb3068 status: Has correction - date: '2014-10-31' doi: 10.1038/ncb942 noticeDoi: 10.1038/ncb3068 status: Retracted id: 81351309 issns: - 1465-7392 - 1476-4679 issue: '3' journal: Nature Cell Biology journalSlug: r6W4d memberId: 297 normalizedTypes: - article page: 224-230 preprintLinks: [] publicationLinks: [] publisher: Springer Science and Business Media LLC retracted: false shortJournal: Nat Cell Biol slug: cytokines-suppress-adipogenesis-and-ppar-vNbgV3 title: >- Cytokines suppress adipogenesis and PPAR-γ function through the TAK1/TAB1/NIK cascade type: journal-article volume: '5' year: 2003 10.1038/nm.1964: authors: - affiliation: University of Tokyo affiliationID: '11716' affiliationSlug: university-of-tokyo-QYyz authorID: '18891380' authorName: Satoshi Nishimura authorSequenceNumber: 1 authorSlug: satoshi-nishimura-l6ZN43 family: Nishimura given: Satoshi - authorID: '6401907' authorName: Ichiro Manabe authorSequenceNumber: 2 authorSlug: ichiro-manabe-YZEjM3 family: Manabe given: Ichiro - affiliation: University of Tokyo affiliationID: '11716' affiliationSlug: university-of-tokyo-QYyz authorID: '9353705' authorName: Mika Nagasaki authorSequenceNumber: 3 authorSlug: mika-nagasaki-AN2nlZ family: Nagasaki given: Mika - affiliation: University of Tokyo affiliationID: '11716' affiliationSlug: university-of-tokyo-QYyz authorID: '9615874' authorName: Koji Eto authorSequenceNumber: 4 authorSlug: koji-eto-pxWeez family: Eto given: Koji - affiliation: University of Tokyo affiliationID: '11716' affiliationSlug: university-of-tokyo-QYyz authorID: '23923457' authorName: Hiroshi Yamashita authorSequenceNumber: 5 authorSlug: hiroshi-yamashita-Gayxab family: Yamashita given: Hiroshi - affiliation: University of Tokyo affiliationID: '11716' affiliationSlug: university-of-tokyo-QYyz authorID: '14720946' authorName: Mitsuru Ohsugi authorSequenceNumber: 6 authorSlug: mitsuru-ohsugi-9DV5G9 family: Ohsugi given: Mitsuru - affiliation: University of Tokyo affiliationID: '11716' affiliationSlug: university-of-tokyo-QYyz authorID: '7024481' authorName: Makoto Otsu authorSequenceNumber: 7 authorSlug: makoto-otsu-jMAG0d family: Otsu given: Makoto - affiliation: University of Tokyo affiliationID: '11716' affiliationSlug: university-of-tokyo-QYyz authorID: '178577914' authorName: Hara Kazuo authorSequenceNumber: 8 authorSlug: hara-kazuo-gZXDjDz family: Kazuo given: Hara - affiliation: University of Tokyo affiliationID: '11716' affiliationSlug: university-of-tokyo-QYyz authorID: '7998801' authorName: Kohjiro Ueki authorSequenceNumber: 9 authorSlug: kohjiro-ueki-PzVp3k family: Ueki given: Kohjiro - affiliation: University of Tokyo affiliationID: '11716' affiliationSlug: university-of-tokyo-QYyz authorID: '17300362' authorName: Seiryo Sugiura authorSequenceNumber: 10 authorSlug: seiryo-sugiura-dOrO93 family: Sugiura given: Seiryo - affiliation: University of Tokyo affiliationID: '11716' affiliationSlug: university-of-tokyo-QYyz authorID: '21167864' authorName: Kotaro Yoshimura authorSequenceNumber: 11 authorSlug: kotaro-yoshimura-y9rmDa family: Yoshimura given: Kotaro - affiliation: University of Tokyo affiliationID: '11716' affiliationSlug: university-of-tokyo-QYyz authorID: '19649000' authorName: Takashi Kadowaki authorSequenceNumber: 12 authorSlug: takashi-kadowaki-3NvpyZ family: Kadowaki given: Takashi - affiliation: University of Tokyo affiliationID: '11716' affiliationSlug: university-of-tokyo-QYyz authorID: '27486996' authorName: Ryozo Nagai authorSequenceNumber: 13 authorSlug: ryozo-nagai-MyRJkW family: Nagai given: Ryozo doi: 10.1038/nm.1964 editorialNotices: [] id: 81413230 issns: - 1078-8956 - 1546-170X issue: '8' journal: Nature Medicine journalSlug: PQ3Xm memberId: 297 normalizedTypes: - article page: 914-920 preprintLinks: [] publicationLinks: [] publisher: Springer Science and Business Media LLC retracted: false shortJournal: Nat Med slug: cd8-effector-t-cells-contribute-ppmP2N title: >- CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity type: journal-article volume: '15' year: 2009 10.1038/nm.2353: abstract: >- Chronic inflammation characterized by T cell and macrophage infiltration of visceral adipose tissue (VAT) is a hallmark of obesity associated insulin resistance and glucose intolerance. Here we demonstrate a fundamental pathogenic role for B cells in the development of these metabolic abnormalities. B cells accumulate in VAT in diet induced obese (DIO) mice, and DIO mice lacking B cells are protected from disease despite weight gain. B cell effects on glucose metabolism are mechanistically linked to activation of pro-inflammatory macrophages and T cells, and production of pathogenic IgG antibodies. Treatment with a B cell-depleting CD20 antibody attenuates disease, while transfer of DIO-IgG rapidly induces insulin resistance and glucose intolerance. Moreover, insulin resistance in obese humans is associated with a unique profile of IgG autoantibodies. These results establish the importance of B cells and adaptive immunity in insulin resistance and suggest new diagnostic and therapeutic modalities to manage the disease. authors: - affiliation: Stanford University affiliationID: '23761' affiliationSlug: stanford-university-EVVW authorID: '193185945' authorName: Daniel A. Winer authorSequenceNumber: 1 authorSlug: daniel-a-winer-PQxdEVR family: Winer given: Daniel A. - affiliation: University of Toronto affiliationID: '12922' affiliationSlug: university-of-toronto-xWjA authorID: '8957022' authorName: Shawn Winer authorSequenceNumber: 2 authorSlug: shawn-winer-xQ9W0A family: Winer given: Shawn - affiliation: Stanford University affiliationID: '23761' affiliationSlug: stanford-university-EVVW authorID: '21345297' authorName: Lei Shen authorSequenceNumber: 3 authorSlug: lei-shen-vZ1vA3 family: Shen given: Lei - affiliation: Stanford University affiliationID: '23761' affiliationSlug: stanford-university-EVVW authorID: '41498331' authorName: Persis P. Wadia authorSequenceNumber: 4 authorSlug: persis-p-wadia-Z9ynyP family: Wadia given: Persis P. - affiliation: University of Toronto affiliationID: '12922' affiliationSlug: university-of-toronto-xWjA authorID: '95448406' authorName: Jason Yantha authorSequenceNumber: 5 authorSlug: jason-yantha-zGvNl5 family: Yantha given: Jason - affiliation: University of Toronto affiliationID: '12922' affiliationSlug: university-of-toronto-xWjA authorID: '5914355' authorName: Geoffrey Paltser authorSequenceNumber: 6 authorSlug: geoffrey-paltser-ejwg4K family: Paltser given: Geoffrey - affiliation: University of Toronto affiliationID: '12922' affiliationSlug: university-of-toronto-xWjA authorID: '20465397' authorName: Hubert Tsui authorSequenceNumber: 7 authorSlug: hubert-tsui-vZAwmO family: Tsui given: Hubert - affiliation: University of Toronto affiliationID: '12922' affiliationSlug: university-of-toronto-xWjA authorID: '34213183' authorName: Ping Wu authorSequenceNumber: 8 authorSlug: ping-wu-aPYG81 family: Wu given: Ping - affiliation: Stanford University affiliationID: '23761' affiliationSlug: stanford-university-EVVW authorID: '80922272' authorName: Matthew G. Davidson authorSequenceNumber: 9 authorSlug: matthew-g-davidson-wN6xWe family: Davidson given: Matthew G. - affiliation: Stanford University affiliationID: '23761' affiliationSlug: stanford-university-EVVW authorID: '14095121' authorName: Michael N. Alonso authorSequenceNumber: 10 authorSlug: michael-n-alonso-8VMlE9 family: Alonso given: Michael N. - affiliation: Stanford University affiliationID: '23761' affiliationSlug: stanford-university-EVVW authorID: '13809772' authorName: Hwei X Leong authorSequenceNumber: 11 authorSlug: hwei-x-leong-wZW31z family: Leong given: Hwei X - affiliation: Stanford University affiliationID: '23761' affiliationSlug: stanford-university-EVVW authorID: '29260441' authorName: Alec J. Glassford authorSequenceNumber: 12 authorSlug: alec-j-glassford-XG8y5x family: Glassford given: Alec J. - affiliation: Stanford University affiliationID: '23761' affiliationSlug: stanford-university-EVVW authorID: '1250253' authorName: Maria Caimol authorSequenceNumber: 13 authorSlug: maria-caimol-vROz2 family: Caimol given: Maria - affiliation: Stanford University affiliationID: '23761' affiliationSlug: stanford-university-EVVW authorID: '9862557' authorName: Justin A. Kenkel authorSequenceNumber: 14 authorSlug: justin-a-kenkel-G5wNA3 family: Kenkel given: Justin A. - affiliation: Duke University affiliationID: '6797' affiliationSlug: duke-university-vxKN authorID: '52059623' authorName: Thomas F. Tedder authorSequenceNumber: 15 authorSlug: thomas-f-tedder-JMk3MG family: Tedder given: Thomas F. - affiliation: Stanford University affiliationID: '23761' affiliationSlug: stanford-university-EVVW authorID: '18132862' authorName: Tracey McLaughlin authorSequenceNumber: 16 authorSlug: tracey-mclaughlin-dOaj9R family: McLaughlin given: Tracey - affiliation: Stanford University affiliationID: '23761' affiliationSlug: stanford-university-EVVW authorID: '7927765' authorName: David B. Miklos authorSequenceNumber: 17 authorSlug: david-b-miklos-8gmgj2 family: Miklos given: David B. - affiliation: University of Toronto affiliationID: '12922' affiliationSlug: university-of-toronto-xWjA authorID: '45908801' authorName: H.-M. Dosch authorSequenceNumber: 18 authorSlug: h-m-dosch-PAjkgm family: Dosch given: H.-M. - affiliation: Stanford University affiliationID: '23761' affiliationSlug: stanford-university-EVVW authorID: '6347955' authorName: Edgar G. Engleman authorSequenceNumber: 19 authorSlug: edgar-g-engleman-ejQR0r family: Engleman given: Edgar G. doi: 10.1038/nm.2353 editorialNotices: [] id: 81413498 issns: - 1078-8956 - 1546-170X issue: '5' journal: Nature Medicine journalSlug: PQ3Xm keywords: - Article memberId: 297 normalizedTypes: - article page: 610-617 preprintLinks: [] publicationLinks: [] publisher: Springer Science and Business Media LLC retracted: false shortJournal: Nat Med slug: b-cells-promote-insulin-resistance-62GY16 title: >- B cells promote insulin resistance through modulation of T cells and production of pathogenic IgG antibodies type: journal-article volume: '17' year: 2011 10.1038/nri2921: abstract: >- The worldwide epidemic of obesity has brought cons iderable attention to research aimed at understanding the biology of adipocytes (fat cells) and the events occurring in adipose tissue (fat) and in the bodies of obese individuals. Accumulating evidence indicates that obesity causes chronic low-grade inflammation and that this contributes to systemic metabolic dysfunction that is associated with obesity-linked disorders. Adipose tissue functions as a key endocrine organ by releasing multiple bioactive substances, known as adipose-derived secreted factors or adipokines, that have pro-inflammatory or anti-inflammatory activities. Dysregulated production or secretion of these adipokines owing to adipose tissue dysfunction can contribute to the pathogenesis of obesity-linked complications. In this Review, we focus on the role of adipokines in inflammatory responses and discuss their potential as regulators of metabolic function. authors: - affiliation: Nagoya University affiliationID: '8173' affiliationSlug: nagoya-university-rLD3 authorID: '25408956' authorName: Noriyuki Ouchi authorSequenceNumber: 1 authorSlug: noriyuki-ouchi-04WLbL family: Ouchi given: Noriyuki - affiliation: Boston University affiliationID: '7891' affiliationSlug: boston-university-11nj authorID: '67379244' authorName: Jennifer L. Parker authorSequenceNumber: 2 authorSlug: jennifer-l-parker-3aVQ5d family: Parker given: Jennifer L. - affiliation: Boston University affiliationID: '7891' affiliationSlug: boston-university-11nj authorID: '10069091' authorName: Jesse J. Lugus authorSequenceNumber: 3 authorSlug: jesse-j-lugus-1gazl0 family: Lugus given: Jesse J. - affiliation: Boston University affiliationID: '7891' affiliationSlug: boston-university-11nj authorID: '141932666' authorName: Kenneth Walsh authorSequenceNumber: 4 authorSlug: kenneth-walsh-xODp3b family: Walsh given: Kenneth doi: 10.1038/nri2921 editorialNotices: [] id: 81483874 issns: - 1474-1733 - 1474-1741 issue: '2' journal: Nature Reviews Immunology journalSlug: lZ5yr keywords: - Article memberId: 297 normalizedTypes: - article page: 85-97 preprintLinks: [] publicationLinks: [] publisher: Springer Science and Business Media LLC retracted: false shortJournal: Nat Rev Immunol slug: adipokines-in-inflammation-and-metabolic-ppPW3w title: Adipokines in inflammation and metabolic disease type: journal-article volume: '11' year: 2011 10.1038/oby.2009.192: abstract: >- Inflammation and insulin resistance associated with visceral obesity are important risk factors for the development of type 2 diabetes, atherosclerosis, and the metabolic syndrome. The 12/15‐lipoxygenase (12/15‐LO) enzyme has been linked to inflammatory changes in blood vessels that precede the development of atherosclerosis. The expression and role of 12/15‐LO in adipocytes have not been evaluated. We found that 12/15‐LO mRNA was dramatically upregulated in white epididymal adipocytes of high‐fat fed mice. 12/15‐LO was poorly expressed in 3T3‐L1 fibroblasts and was upregulated during differentiation into adipocytes. Interestingly, the saturated fatty acid palmitate, a major component of high fat diets, augmented expression of 12/15‐LO in vitro. When 3T3‐L1 adipocytes were treated with the 12/15‐LO products, 12‐hydroxyeicosatetranoic acid (12(S)‐HETE) and 12‐hydroperoxyeicosatetraenoic acid (12(S)‐HPETE), expression of proinflammatory cytokine genes, including tumor necrosis factor‐α (TNF‐α), monocyte chemoattractant protein 1 (MCP‐1), interleukin 6 (IL‐6), and IL‐12p40, was upregulated whereas anti‐inflammatory adiponectin gene expression was downregulated. 12/15‐LO products also augmented c‐Jun N‐terminal kinase 1 (JNK‐1) phosphorylation, a known negative regulator of insulin signaling. Consistent with impaired insulin signaling, we found that insulin‐stimulated 3T3‐L1 adipocytes exhibited decreased IRS‐1(Tyr) phosphorylation, increased IRS‐1(Ser) phosphorylation, and impaired Akt phosphorylation when treated with 12/15‐LO product. Taken together, our data suggest that 12/15‐LO products create a proinflammatory state and impair insulin signaling in 3T3‐L1 adipocytes. Because 12/15‐LO expression is upregulated in visceral adipocytes by high‐fat feeding in vivo and also by addition of palmitic acid in vitro, we propose that 12/15‐LO plays a role in promoting inflammation and insulin resistance associated with obesity. authors: - affiliation: Eastern Virginia Medical School affiliationID: '382' affiliationSlug: eastern-virginia-medical-school-VLP authorID: '63079324' authorName: Swarup K. Chakrabarti authorSequenceNumber: 1 authorSlug: swarup-k-chakrabarti-kEaKjX family: Chakrabarti given: Swarup K. - affiliation: Eastern Virginia Medical School affiliationID: '382' affiliationSlug: eastern-virginia-medical-school-VLP authorID: '12170150' authorName: Banumathi K. Cole authorSequenceNumber: 2 authorSlug: banumathi-k-cole-zL3839 family: Cole given: Banumathi K. - affiliation: University of Virginia affiliationID: '26257' affiliationSlug: university-of-virginia-GAeJ authorID: '54942341' authorName: Yeshao Wen authorSequenceNumber: 3 authorSlug: yeshao-wen-XOmWlw family: Wen given: Yeshao - affiliation: University of Virginia affiliationID: '26257' affiliationSlug: university-of-virginia-GAeJ authorID: '19537263' authorName: Susanna R. Keller authorSequenceNumber: 4 authorSlug: susanna-r-keller-DROWMN family: Keller given: Susanna R. - affiliation: Eastern Virginia Medical School affiliationID: '382' affiliationSlug: eastern-virginia-medical-school-VLP authorID: '16259863' authorName: Jerry L. Nadler authorSequenceNumber: 5 authorSlug: jerry-l-nadler-DmQA4W family: Nadler given: Jerry L. doi: 10.1038/oby.2009.192 editorialNotices: [] id: 81510862 issns: - 1930-7381 issue: '9' journal: Obesity journalSlug: V01EE keywords: - Article memberId: 311 normalizedTypes: - article page: 1657-1663 preprintLinks: [] publicationLinks: [] publisher: Wiley retracted: false slug: 12-15-lipoxygenase-products-induce-inflammation-and-dl8jmy title: >- 12/15-Lipoxygenase Products Induce Inflammation and Impair Insulin Signaling in 3T3-L1 Adipocytes type: journal-article volume: '17' year: 2009 10.1038/s41598-017-06397-4: abstract: >- Eosinophils and their associated cytokines IL-4 and IL-5 are emerging as central orchestrators of the immune-metabolic axis. Herein, we demonstrate that cross-talk between the Ig-superfamily receptor CD300f and IL-5 is a key checkpoint that modifies the ability of eosinophils to regulate metabolic outcomes. Generation of Il5 Tg /Cd300f −/− mice revealed marked and distinct increases in eosinophil levels and their production of IL-4 in the white and brown adipose tissues. Consequently, Il5 Tg /Cd300f −/− mice had increased alternatively activated macrophage accumulation in the adipose tissue. Cd300f −/− mice displayed age-related accumulation of eosinophils and macrophages in the adipose tissue and decreased adipose tissue weight, which was associated with decreased diet-induced weight gain and insulin resistance. Notably, Il5 Tg /CD300f −/− were protected from diet-induced weight gain and glucose intolerance. These findings highlight the cross-talk between IL-5 receptor and CD300f as a novel pathway regulating adipose tissue eosinophils and offer new entry points for therapeutic intervention for obesity and its complications. authors: - affiliation: Tel Aviv University affiliationID: '12679' affiliationSlug: tel-aviv-university-KPbp authorID: '11006029' authorName: Perri Rozenberg authorSequenceNumber: 1 authorSlug: perri-rozenberg-rx4Y46 family: Rozenberg given: Perri - affiliation: Tel Aviv University affiliationID: '12679' affiliationSlug: tel-aviv-university-KPbp authorID: '28124321' authorName: Hadar Reichman authorSequenceNumber: 2 authorSlug: hadar-reichman-86K6Gm family: Reichman given: Hadar - affiliation: Tel Aviv University affiliationID: '12679' affiliationSlug: tel-aviv-university-KPbp authorID: '131934550' authorName: Israel Zab-Bar authorSequenceNumber: 3 authorSlug: israel-zab-bar-zypaVK family: Zab-Bar given: Israel - affiliation: Tel Aviv University affiliationID: '12679' affiliationSlug: tel-aviv-university-KPbp authorID: '5216739' authorName: Michal Itan authorSequenceNumber: 4 authorSlug: michal-itan-aXkmEv family: Itan given: Michal - affiliation: Tel Aviv University affiliationID: '12679' affiliationSlug: tel-aviv-university-KPbp authorID: '14034264' authorName: Metsada Pasmanik-Chor authorSequenceNumber: 5 authorSlug: metsada-pasmanik-chor-yg6YJG family: Pasmanik-Chor given: Metsada - affiliation: Cincinnati Children's Hospital Medical Center affiliationID: '16374' affiliationSlug: cincinnati-children-s-hospital-medical-center-pADQ authorID: '297869' authorName: Carine Bouffi authorSequenceNumber: 6 authorSlug: carine-bouffi-5M2WA family: Bouffi given: Carine - affiliation: Tel Aviv University affiliationID: '12679' affiliationSlug: tel-aviv-university-KPbp authorID: '1662244' authorName: Udi Qimron authorSequenceNumber: 7 authorSlug: udi-qimron-3Gkwy family: Qimron given: Udi - authorID: '7517075' authorName: Ido Bachelet authorSequenceNumber: 8 authorSlug: ido-bachelet-ZxQm0r family: Bachelet given: Ido - affiliation: Cincinnati Children's Hospital Medical Center affiliationID: '16374' affiliationSlug: cincinnati-children-s-hospital-medical-center-pADQ authorID: '7740496' authorName: Patricia C. Fulkerson authorSequenceNumber: 9 authorSlug: patricia-c-fulkerson-M22g0m family: Fulkerson given: Patricia C. - affiliation: Cincinnati Children's Hospital Medical Center affiliationID: '16374' affiliationSlug: cincinnati-children-s-hospital-medical-center-pADQ authorID: '11358116' authorName: Marc E. Rothenberg authorSequenceNumber: 10 authorSlug: marc-e-rothenberg-QmeOgJ family: Rothenberg given: Marc E. - affiliation: Tel Aviv University affiliationID: '12679' affiliationSlug: tel-aviv-university-KPbp authorID: '121132203' authorName: Ariel Munitz authorSequenceNumber: 11 authorSlug: ariel-munitz-19xRJy family: Munitz given: Ariel doi: 10.1038/s41598-017-06397-4 editorialNotices: [] id: 233718020 issns: - 2045-2322 issue: '1' journal: Scientific Reports journalSlug: n6W5k keywords: - Article memberId: 297 normalizedTypes: - article preprintLinks: [] publicationLinks: [] publisher: Springer Science and Business Media LLC retracted: false shortJournal: Sci Rep slug: cd300f-il-5-cross-talk-inhibits-adipose-tissue-y8Q5z9p title: >- CD300f:IL-5 cross-talk inhibits adipose tissue eosinophil homing and subsequent IL-4 production type: journal-article volume: '7' year: 2017 10.1038/s41598-018-28371-4: abstract: >- Accumulating data have indicated a fundamental role of eosinophils in regulating adipose tissue homeostasis. Here, we performed whole-genome RNA sequencing of the small intestinal tract, which suggested the presence of impaired lipid metabolism in eosinophil-deficient ΔdblGATA mice. ΔdblGATA mice fed a high-fat diet (HFD) showed reduced body fat mass, impaired enlargement of adipocytes, decreased expression of adipogenic genes, and developed glucose intolerance. HFD induced accumulation of eosinophils in the perigonadal white adipose tissue. Concordantly, adipocyte-differentiated 3T3-L1 cells promoted the migration of eosinophils through the expression of CCL11 (eotaxin-1) and likely promoted their survival through the expression of interleukin (IL)-3, IL-5, and granulocyte-macrophage colony-stimulating factor. HFD-fed ΔdblGATA mice showed increased infiltration of macrophages, CD4+ T-cells, and B-cells, increased expression of interferon-γ, and decreased expression of IL-4 and IL-13 in white adipose tissue. Interferon-γ treatment significantly decreased lipid deposition in adipocyte-differentiated 3T3-L1 cells, while IL-4 treatment promoted lipid accumulation. Notably, HFD-fed ΔdblGATA mice showed increased lipid storage in the liver as compared with wild-type mice. We propose that obesity promotes the infiltration of eosinophils into adipose tissue that subsequently contribute to the metabolic homeostasis by promoting adipocyte maturation. authors: - affiliation: Gachon University affiliationID: '9120' affiliationSlug: gachon-university-yJdl authorID: '152962979' authorName: Eun-Hui Lee authorSequenceNumber: 1 authorSlug: eun-hui-lee-KQMmMe family: Lee given: Eun-Hui - affiliation: Tel Aviv University affiliationID: '12679' affiliationSlug: tel-aviv-university-KPbp authorID: '5216739' authorName: Michal Itan authorSequenceNumber: 2 authorSlug: michal-itan-aXkmEv family: Itan given: Michal - affiliation: Gachon University affiliationID: '9120' affiliationSlug: gachon-university-yJdl authorID: '152979076' authorName: Jinsun Jang authorSequenceNumber: 3 authorSlug: jinsun-jang-2Zd5bY family: Jang given: Jinsun - affiliation: Gachon University affiliationID: '9120' affiliationSlug: gachon-university-yJdl authorID: '152933925' authorName: Hyeon-Jung Gu authorSequenceNumber: 4 authorSlug: hyeon-jung-gu-5O8x8G family: Gu given: Hyeon-Jung - affiliation: Tel Aviv University affiliationID: '12679' affiliationSlug: tel-aviv-university-KPbp authorID: '11006029' authorName: Perri Rozenberg authorSequenceNumber: 5 authorSlug: perri-rozenberg-rx4Y46 family: Rozenberg given: Perri - affiliation: Cincinnati Children's Hospital Medical Center affiliationID: '16374' affiliationSlug: cincinnati-children-s-hospital-medical-center-pADQ authorID: '4965324' authorName: Melissa K. Mingler authorSequenceNumber: 6 authorSlug: melissa-k-mingler-kenLwL family: Mingler given: Melissa K. - affiliation: Cincinnati Children's Hospital Medical Center affiliationID: '16374' affiliationSlug: cincinnati-children-s-hospital-medical-center-pADQ authorID: '17384861' authorName: Ting Wen authorSequenceNumber: 7 authorSlug: ting-wen-EOXp5P family: Wen given: Ting - affiliation: Gachon University affiliationID: '9120' affiliationSlug: gachon-university-yJdl authorID: '38694820' authorName: Jiyoung Yoon authorSequenceNumber: 8 authorSlug: jiyoung-yoon-ywPwN6 family: Yoon given: Jiyoung - affiliation: Gachon University affiliationID: '9120' affiliationSlug: gachon-university-yJdl authorID: '52112172' authorName: Shi-Young Park authorSequenceNumber: 9 authorSlug: shi-young-park-wXpAje family: Park given: Shi-Young - affiliation: Gachon University affiliationID: '9120' affiliationSlug: gachon-university-yJdl authorID: '12711292' authorName: Joo Young Roh authorSequenceNumber: 10 authorSlug: joo-young-roh-WxV0zQ family: Roh given: Joo Young - affiliation: Gachon University affiliationID: '9120' affiliationSlug: gachon-university-yJdl authorID: '8946745' authorName: Cheol Soo Choi authorSequenceNumber: 11 authorSlug: cheol-soo-choi-PzKQ1V family: Choi given: Cheol Soo - affiliation: Gachon University affiliationID: '9120' affiliationSlug: gachon-university-yJdl authorID: '152936204' authorName: Woo-Jae Park authorSequenceNumber: 12 authorSlug: woo-jae-park-Wwy42O family: Park given: Woo-Jae - affiliation: Tel Aviv University affiliationID: '12679' affiliationSlug: tel-aviv-university-KPbp authorID: '121132203' authorName: Ariel Munitz authorSequenceNumber: 13 authorSlug: ariel-munitz-19xRJy family: Munitz given: Ariel - affiliation: Gachon University affiliationID: '9120' affiliationSlug: gachon-university-yJdl authorID: '139679076' authorName: Yun-Jae Jung authorSequenceNumber: 14 authorSlug: yun-jae-jung-2PO1JE family: Jung given: Yun-Jae doi: 10.1038/s41598-018-28371-4 editorialNotices: [] id: 223144610 issns: - 2045-2322 issue: '1' journal: Scientific Reports journalSlug: n6W5k keywords: - Article memberId: 297 normalizedTypes: - article preprintLinks: [] publicationLinks: [] publisher: Springer Science and Business Media LLC retracted: false shortJournal: Sci Rep slug: eosinophils-support-adipocyte-maturation-and-68jbdR1 title: >- Eosinophils support adipocyte maturation and promote glucose tolerance in obesity type: journal-article volume: '8' year: 2018 10.1053/j.gastro.2013.04.010: abstract: >- BACKGROUND & AIMS An increased number of macrophages in adipose tissue is associated with insulin resistance and metabolic dysfunction in obese people. However, little is known about other immune cells in adipose tissue from obese people, and whether they contribute to insulin resistance. We investigated the characteristics of T cells in adipose tissue from metabolically abnormal insulin-resistant obese (MAO) subjects, metabolically normal insulin-sensitive obese (MNO) subjects, and lean subjects. Insulin sensitivity was determined by using the hyperinsulinemic euglycemic clamp procedure. METHODS We assessed plasma cytokine concentrations and subcutaneous adipose tissue CD4+ T-cell populations in 9 lean, 12 MNO, and 13 MAO subjects. Skeletal muscle and liver samples were collected from 19 additional obese patients undergoing bariatric surgery to determine the presence of selected cytokine receptors. RESULTS Adipose tissue from MAO subjects had 3- to 10-fold increases in numbers of CD4+ T cells that produce interleukin (IL)-22 and IL-17 (a T-helper [Th] 17 and Th22 phenotype) compared with MNO and lean subjects. MAO subjects also had increased plasma concentrations of IL-22 and IL-6. Receptors for IL-17 and IL-22 were expressed in human liver and skeletal muscle samples. IL-17 and IL-22 inhibited uptake of glucose in skeletal muscle isolated from rats and reduced insulin sensitivity in cultured human hepatocytes. CONCLUSIONS Adipose tissue from MAO individuals contains increased numbers of Th17 and Th22 cells, which produce cytokines that cause metabolic dysfunction in liver and muscle in vitro. Additional studies are needed to determine whether these alterations in adipose tissue T cells contribute to the pathogenesis of insulin resistance in obese people. authors: - affiliation: Washington University in St. Louis affiliationID: '19037' affiliationSlug: washington-university-in-st-louis-jjaJ authorID: '6328562' authorName: Elisa Fabbrini authorSequenceNumber: 1 authorSlug: elisa-fabbrini-dvbLj1 family: Fabbrini given: Elisa - affiliation: Washington University in St. Louis affiliationID: '19037' affiliationSlug: washington-university-in-st-louis-jjaJ authorID: '19860613' authorName: Marina Cella authorSequenceNumber: 2 authorSlug: marina-cella-G6AaLL family: Cella given: Marina - affiliation: Washington University in St. Louis affiliationID: '19037' affiliationSlug: washington-university-in-st-louis-jjaJ authorID: '64542774' authorName: Steve A. Mccartney authorSequenceNumber: 3 authorSlug: steve-a-mccartney-pVLNLw family: Mccartney given: Steve A. - affiliation: Washington University in St. Louis affiliationID: '19037' affiliationSlug: washington-university-in-st-louis-jjaJ authorID: '8082696' authorName: Anja Fuchs authorSequenceNumber: 4 authorSlug: anja-fuchs-M21g8X family: Fuchs given: Anja - affiliation: Washington University in St. Louis affiliationID: '19037' affiliationSlug: washington-university-in-st-louis-jjaJ authorID: '1846449' authorName: Nada A. Abumrad authorSequenceNumber: 5 authorSlug: nada-a-abumrad-A2edE family: Abumrad given: Nada A. - affiliation: Washington University in St. Louis affiliationID: '19037' affiliationSlug: washington-university-in-st-louis-jjaJ authorID: '10659883' authorName: Terri A. Pietka authorSequenceNumber: 6 authorSlug: terri-a-pietka-ayennj family: Pietka given: Terri A. - affiliation: Washington University in St. Louis affiliationID: '19037' affiliationSlug: washington-university-in-st-louis-jjaJ authorID: '13723397' authorName: Zhouji Chen authorSequenceNumber: 7 authorSlug: zhouji-chen-vxOdk3 family: Chen given: Zhouji - affiliation: Washington University in St. Louis affiliationID: '19037' affiliationSlug: washington-university-in-st-louis-jjaJ authorID: '22224481' authorName: Brian N. Finck authorSequenceNumber: 8 authorSlug: brian-n-finck-jzYEOy family: Finck given: Brian N. - affiliation: Washington University in St. Louis affiliationID: '19037' affiliationSlug: washington-university-in-st-louis-jjaJ authorID: '154715410' authorName: Dong Ho Han authorSequenceNumber: 9 authorSlug: dong-ho-han-6aL9xE family: Han given: Dong Ho - affiliation: Washington University in St. Louis affiliationID: '19037' affiliationSlug: washington-university-in-st-louis-jjaJ authorID: '865583' authorName: Faidon Magkos authorSequenceNumber: 10 authorSlug: faidon-magkos-amb81 family: Magkos given: Faidon - affiliation: Sapienza University of Rome affiliationID: '7808' affiliationSlug: sapienza-university-of-rome-MlVW authorID: '147884582' authorName: Caterina Conte authorSequenceNumber: 11 authorSlug: caterina-conte-VlGK1W family: Conte given: Caterina - affiliation: Washington University in St. Louis affiliationID: '19037' affiliationSlug: washington-university-in-st-louis-jjaJ authorID: '19312583' authorName: Steven M. Bradley authorSequenceNumber: 12 authorSlug: steven-m-bradley-aYn5R1 family: Bradley given: Steven M. - affiliation: Washington University in St. Louis affiliationID: '19037' affiliationSlug: washington-university-in-st-louis-jjaJ authorID: '15028188' authorName: David Bradley authorSequenceNumber: 12 authorSlug: david-bradley-3KA3LW family: Bradley given: David - affiliation: Washington University in St. Louis affiliationID: '19037' affiliationSlug: washington-university-in-st-louis-jjaJ authorID: '28339390' authorName: Gemma Fraterrigo authorSequenceNumber: 13 authorSlug: gemma-fraterrigo-9x84Rb family: Fraterrigo given: Gemma - affiliation: Washington University in St. Louis affiliationID: '19037' affiliationSlug: washington-university-in-st-louis-jjaJ authorID: '2597312' authorName: J. Christopher Eagon authorSequenceNumber: 14 authorSlug: j-christopher-eagon-0V2gZ family: Eagon given: J. Christopher - affiliation: Washington University in St. Louis affiliationID: '19037' affiliationSlug: washington-university-in-st-louis-jjaJ authorID: '17244299' authorName: Bruce W. Patterson authorSequenceNumber: 15 authorSlug: bruce-w-patterson-eD8zK0 family: Patterson given: Bruce W. - affiliation: Washington University in St. Louis affiliationID: '19037' affiliationSlug: washington-university-in-st-louis-jjaJ authorID: '9938079' authorName: Marco Colonna authorSequenceNumber: 16 authorSlug: marco-colonna-KWXmvd family: Colonna given: Marco - affiliation: Washington University in St. Louis affiliationID: '19037' affiliationSlug: washington-university-in-st-louis-jjaJ authorID: '13449418' authorName: Samuel Klein authorSequenceNumber: 17 authorSlug: samuel-klein-dKZeXy family: Klein given: Samuel doi: 10.1053/j.gastro.2013.04.010 editorialNotices: [] id: 83257460 issns: - 0016-5085 issue: '2' journal: Gastroenterology journalSlug: pnmJj keywords: - Article memberId: 78 normalizedTypes: - article page: 366-374.e3 preprintLinks: [] publicationLinks: [] publisher: Elsevier BV retracted: false shortJournal: Gastroenterology slug: association-between-specific-adipose-tissue-QpEVZJ title: >- Association Between Specific Adipose Tissue CD4+ T-Cell Populations and Insulin Resistance in Obese Individuals type: journal-article volume: '145' year: 2013 10.1074/jbc.275.12.8456: abstract: >- Insulin resistance is a major factor in the pathogenesis of type 2 diabetes and may be related to alterations in fat metabolism. Fatless mice have been created using dominant-negative protein (A-ZIP/F-1) targeted gene expression in the adipocyte and shown to develop diabetes. To understand the mechanism responsible for the insulin resistance in these mice, we conducted hyperinsulinemic-euglycemic clamps in awake fatless and wild type littermates before the development of diabetes and examined insulin action and signaling in muscle and liver. We found the fatless mice to be severely insulinresistant, which could be attributed to defects in insulin action in muscle and liver. Both of these abnormalities were associated with defects in insulin activation of insulin receptor substrate-1 and -2-associated phosphatidylinositol 3-kinase activity and a 2-fold increase in muscle and liver triglyceride content. We also show that upon transplantation of fat tissue into these mice, triglyceride content in muscle and liver returned to normal as does insulin signaling and action. In conclusion, these results suggest that the development of insulin resistance in type 2 diabetes may be due to alterations in the partitioning of fat between the adipocyte and muscle/liver leading to accumulation of triglyceride in the latter tissues with subsequent impairment of insulin signaling and action. authors: - affiliation: Yale University affiliationID: '8068' affiliationSlug: yale-university-kyQE authorID: '15023009' authorName: Jason K. Kim authorSequenceNumber: 1 authorSlug: jason-k-kim-vdg5aJ family: Kim given: Jason K. - affiliation: National Institutes of Health affiliationID: '26753' affiliationSlug: national-institutes-of-health-vVaJ authorID: '17567133' authorName: Oksana Gavrilova authorSequenceNumber: 2 authorSlug: oksana-gavrilova-nz5X46 family: Gavrilova given: Oksana - affiliation: Yale University affiliationID: '8068' affiliationSlug: yale-university-kyQE authorID: '92152483' authorName: Yan Chen authorSequenceNumber: 3 authorSlug: yan-chen-aZwp6r family: Chen given: Yan - affiliation: National Institutes of Health affiliationID: '26753' affiliationSlug: national-institutes-of-health-vVaJ authorID: '6596888' authorName: Marc L. Reitman authorSequenceNumber: 4 authorSlug: marc-l-reitman-3n1GLy family: Reitman given: Marc L. - affiliation: Yale University affiliationID: '8068' affiliationSlug: yale-university-kyQE authorID: '5886223' authorName: Gerald I. Shulman authorSequenceNumber: 5 authorSlug: gerald-i-shulman-J1LvKY family: Shulman given: Gerald I. doi: 10.1074/jbc.275.12.8456 editorialNotices: [] id: 85706041 issns: - 0021-9258 issue: '12' journal: Journal of Biological Chemistry journalSlug: MVW30 memberId: 78 normalizedTypes: - article page: 8456-8460 preprintLinks: [] publicationLinks: [] publisher: Elsevier BV retracted: false shortJournal: Journal of Biological Chemistry slug: mechanism-of-insulin-resistance-in-XR5Emw title: Mechanism of Insulin Resistance in A-ZIP/F-1 Fatless Mice type: journal-article volume: '275' year: 2000 10.1074/jbc.m109.061655: abstract: >- Recent reports demonstrate T-cell infiltration of adipose tissue in early obesity. We hypothesized that interferon (IFN) ␥, a major T-cell inflammatory cytokine, would attenuate human adipocyte functions and sought to establish signaling mechanisms. Differentiated human adipocytes were treated with IFN␥ ؎ pharmacological inhibitors prior to insulin stimulation. authors: - affiliation: University of Pennsylvania affiliationID: '15362' affiliationSlug: university-of-pennsylvania-dN49 authorID: '8092877' authorName: Fiona C. McGillicuddy authorSequenceNumber: 1 authorSlug: fiona-c-mcgillicuddy-ngJQX6 family: McGillicuddy given: Fiona C. - affiliation: Cardiovascular Institute of the South affiliationID: '5887' affiliationSlug: cardiovascular-institute-of-the-south-meOY authorID: '104629' authorName: Elise H. Chiquoine authorSequenceNumber: 2 authorSlug: elise-h-chiquoine-r6j64 family: Chiquoine given: Elise H. - affiliation: Cardiovascular Institute of the South affiliationID: '5887' affiliationSlug: cardiovascular-institute-of-the-south-meOY authorID: '10676726' authorName: Christine C. Hinkle authorSequenceNumber: 3 authorSlug: christine-c-hinkle-R5nOrD family: Hinkle given: Christine C. - affiliation: Children's Hospital of Philadelphia affiliationID: '25227' affiliationSlug: children-s-hospital-of-philadelphia-N0lg authorID: '20859841' authorName: Roy J. Kim authorSequenceNumber: 4 authorSlug: roy-j-kim-XEa5Ql family: Kim given: Roy J. - affiliation: Children's Hospital of Philadelphia affiliationID: '25227' affiliationSlug: children-s-hospital-of-philadelphia-N0lg authorID: '12514307' authorName: Rachana Shah authorSequenceNumber: 5 authorSlug: rachana-shah-YD4pyD family: Shah given: Rachana - affiliation: University College Dublin affiliationID: '6020' affiliationSlug: university-college-dublin-ygJa authorID: '15444403' authorName: Helen M. Roche authorSequenceNumber: 6 authorSlug: helen-m-roche-115v4W family: Roche given: Helen M. - affiliation: University of Pennsylvania affiliationID: '15362' affiliationSlug: university-of-pennsylvania-dN49 authorID: '8509012' authorName: Emer M. Smyth authorSequenceNumber: 7 authorSlug: emer-m-smyth-0aOj4y family: Smyth given: Emer M. - affiliation: Cardiovascular Institute of the South affiliationID: '5887' affiliationSlug: cardiovascular-institute-of-the-south-meOY authorID: '14621088' authorName: Muredach P. Reilly authorSequenceNumber: 8 authorSlug: muredach-p-reilly-3MPJrd family: Reilly given: Muredach P. doi: 10.1074/jbc.m109.061655 editorialNotices: [] id: 85722044 issns: - 0021-9258 issue: '46' journal: Journal of Biological Chemistry journalSlug: MVW30 memberId: 78 normalizedTypes: - article page: 31936-31944 preprintLinks: [] publicationLinks: [] publisher: Elsevier BV retracted: false shortJournal: Journal of Biological Chemistry slug: interferon-attenuates-insulin-signaling-3kRe2y title: >- Interferon γ Attenuates Insulin Signaling, Lipid Storage, and Differentiation in Human Adipocytes via Activation of the JAK/STAT Pathway type: journal-article volume: '284' year: 2009 10.1074/jbc.m114.628487: authors: - authorID: '15368351' authorName: R. Grace Walton authorSequenceNumber: 1 authorSlug: r-grace-walton-YXX9NE family: Walton given: R. Grace - authorID: '72555609' authorName: Beibei Zhu authorSequenceNumber: 2 authorSlug: beibei-zhu-vn5WxZ family: Zhu given: Beibei - affiliation: Muğla University affiliationID: '25281' affiliationSlug: mugla-university-jd6O authorID: '14893089' authorName: Resat Unal authorSequenceNumber: 3 authorSlug: resat-unal-PD5NMb family: Unal given: Resat - authorID: '20249405' authorName: Michael L. Spencer authorSequenceNumber: 4 authorSlug: michael-l-spencer-AOakaE family: Spencer given: Michael L. - authorID: '8655003' authorName: Manjula Sunkara authorSequenceNumber: 5 authorSlug: manjula-sunkara-1gvwGy family: Sunkara given: Manjula - authorID: '13056434' authorName: Andrew J. Morris authorSequenceNumber: 6 authorSlug: andrew-j-morris-OMeWVA family: Morris given: Andrew J. - authorID: '16010415' authorName: Richard Charnigo authorSequenceNumber: 7 authorSlug: richard-charnigo-bj6408 family: Charnigo given: Richard - authorID: '12419796' authorName: Wendy S. Katz authorSequenceNumber: 8 authorSlug: wendy-s-katz-Mae60l family: Katz given: Wendy S. - affiliation: University of Kentucky affiliationID: '15265' affiliationSlug: university-of-kentucky-86Z3 authorID: '25982711' authorName: Alan Daugherty authorSequenceNumber: 9 authorSlug: alan-daugherty-e14XaK family: Daugherty given: Alan - affiliation: University of Kentucky affiliationID: '15265' affiliationSlug: university-of-kentucky-86Z3 authorID: '201658' authorName: Deborah A. Howatt authorSequenceNumber: 10 authorSlug: deborah-a-howatt-g1jRA family: Howatt given: Deborah A. - authorID: '50346380' authorName: Philip A. Kern authorSequenceNumber: 11 authorSlug: philip-a-kern-ldGZgv family: Kern given: Philip A. - authorID: '24271720' authorName: Brian S. Finlin authorSequenceNumber: 12 authorSlug: brian-s-finlin-yAM4ZR family: Finlin given: Brian S. doi: 10.1074/jbc.m114.628487 editorialNotices: [] id: 85742367 issns: - 0021-9258 issue: '18' journal: Journal of Biological Chemistry journalSlug: MVW30 memberId: 78 normalizedTypes: - article page: 11547-11556 preprintLinks: [] publicationLinks: [] publisher: Elsevier BV retracted: false shortJournal: Journal of Biological Chemistry slug: increasing-adipocyte-lipoprotein-lipase-improves-JQegAn title: >- Increasing Adipocyte Lipoprotein Lipase Improves Glucose Metabolism in High Fat Diet-induced Obesity type: journal-article volume: '290' year: 2015 10.1080/2162402x.2015.1056442: abstract: >- Hypoxia is a common feature of solid tumors, particularly in glioblastoma (GBM), and known to be a poor prognosis factor in GBM patients. The growth of GBM is also associated with a marked inflammation partially characterized by an accumulation of macrophage (MΦ) of the M2 phenotype. However, the transition between M1 MΦ (antitumoral) and M2 MΦ (protumoral) phenotypes is a dynamic process. We made the assumption that oxygen (O2) availability could be a major regulator of this transition and that the intratumoral O2 gradient is of importance. We evaluated, in vivo, the impact of hypoxia on MΦ tropism and polarization in two models of human GBM, well differentiated by their degree of hypoxia. MΦ migration in the tumor was more pronounced in the more hypoxic tumor of the two GBM models. In the more hypoxic of the models, we have shown that MΦ migrated at the tumor site only when hypoxia takes place. We also demonstrated that the acquisition of the M2 phenotype was clearly an evolving phenomenon with hypoxia as the major trigger for this transition. In support of these in vivo finding, M0 but also M1 MΦ cultured in moderate or severe hypoxia displayed a phenotype close to that of M2 MΦ whose phenotype was further reinforced by severe hypoxia. These results highlight the role of hypoxia in the aggressiveness of GBM, in part, by transforming MΦ such that a protumoral activity is expressed. authors: - authorID: '10811488' authorName: M.M. Leblond authorSequenceNumber: 1 authorSlug: m-m-leblond-38R2GJ family: Leblond given: M.M. - authorID: '8445599' authorName: Aurélie N. Gérault authorSequenceNumber: 2 authorSlug: aurelie-n-gerault-eP21Vz family: Gérault given: Aurélie N. - authorID: '66161215' authorName: Aurélien Corroyer-Dulmont authorSequenceNumber: 3 authorSlug: aurelien-corroyer-dulmont-bmgGNk family: Corroyer-Dulmont given: Aurélien - authorID: '14725421' authorName: Eric T. MacKenzie authorSequenceNumber: 4 authorSlug: eric-t-mackenzie-8VjZn9 family: MacKenzie given: Eric T. - authorID: '18194196' authorName: Edwige Petit authorSequenceNumber: 5 authorSlug: edwige-petit-MlwLkW family: Petit given: Edwige - authorID: '8501403' authorName: Myriam Bernaudin authorSequenceNumber: 6 authorSlug: myriam-bernaudin-1gXEKM family: Bernaudin given: Myriam - authorID: '27051663' authorName: Samuel Valable authorSequenceNumber: 7 authorSlug: samuel-valable-DjOMGz family: Valable given: Samuel doi: 10.1080/2162402x.2015.1056442 editorialNotices: [] id: 88644956 issns: - 2162-402X issue: '1' journal: OncoImmunology journalSlug: zR0j9 keywords: - Original Research memberId: 301 normalizedTypes: - article page: e1056442 preprintLinks: [] publicationLinks: [] publisher: Informa UK Limited retracted: false shortJournal: OncoImmunology slug: hypoxia-induces-macrophage-polarization-and-0vyDV9 title: >- Hypoxia induces macrophage polarization and re-education toward an M2 phenotype in U87 and U251 glioblastoma models type: journal-article volume: '5' year: 2015 10.1091/mbc.e02-02-0105: abstract: >- Much of the work conducted on adult stem cells has focused on mesenchymal stem cells (MSCs) found within the bone marrow stroma. Adipose tissue, like bone marrow, is derived from the embryonic mesenchyme and contains a stroma that is easily isolated. Preliminary studies have recently identified a putative stem cell population within the adipose stromal compartment. This cell population, termed processed lipoaspirate (PLA) cells, can be isolated from human lipoaspirates and, like MSCs, differentiate toward the osteogenic, adipogenic, myogenic, and chondrogenic lineages. To confirm whether adipose tissue contains stem cells, the PLA population and multiple clonal isolates were analyzed using several molecular and biochemical approaches. PLA cells expressed multiple CD marker antigens similar to those observed on MSCs. Mesodermal lineage induction of PLA cells and clones resulted in the expression of multiple lineage-specific genes and proteins. Furthermore, biochemical analysis also confirmed lineage-specific activity. In addition to mesodermal capacity, PLA cells and clones differentiated into putative neurogenic cells, exhibiting a neuronal-like morphology and expressing several proteins consistent with the neuronal phenotype. Finally, PLA cells exhibited unique characteristics distinct from those seen in MSCs, including differences in CD marker profile and gene expression. authors: - affiliation: University of California, Los Angeles affiliationID: '16569' affiliationSlug: university-of-california-los-angeles-5eED authorID: '10904548' authorName: Patricia A. Zuk authorSequenceNumber: 1 authorSlug: patricia-a-zuk-WGwQR1 family: Zuk given: Patricia A. - affiliation: University of California, Los Angeles affiliationID: '16569' affiliationSlug: university-of-california-los-angeles-5eED authorID: '214178751' authorName: Min Zhu authorSequenceNumber: 2 authorSlug: min-zhu-YZbjbV3 family: Zhu given: Min - affiliation: University of California, Los Angeles affiliationID: '16569' affiliationSlug: university-of-california-los-angeles-5eED authorID: '6176633' authorName: Peter Ashjian authorSequenceNumber: 3 authorSlug: peter-ashjian-n6RKm6 family: Ashjian given: Peter - affiliation: University of California, Los Angeles affiliationID: '16569' affiliationSlug: university-of-california-los-angeles-5eED authorID: '32143121' authorName: Daniel A. De Ugarte authorSequenceNumber: 4 authorSlug: daniel-a-de-ugarte-88xJY2 family: Ugarte given: Daniel A. De - affiliation: University of California, Los Angeles affiliationID: '16569' affiliationSlug: university-of-california-los-angeles-5eED authorID: '31478953' authorName: Jerry I. Huang authorSequenceNumber: 5 authorSlug: jerry-i-huang-vp3kzW family: Huang given: Jerry I. - affiliation: University of California, Los Angeles affiliationID: '16569' affiliationSlug: university-of-california-los-angeles-5eED authorID: '31856060' authorName: Hiroshi Mizuno authorSequenceNumber: 6 authorSlug: hiroshi-mizuno-QQGRLV family: Mizuno given: Hiroshi - affiliation: University of California, Los Angeles affiliationID: '16569' affiliationSlug: university-of-california-los-angeles-5eED authorID: '8164751' authorName: Zeni Alfonso authorSequenceNumber: 7 authorSlug: zeni-alfonso-YgK14L family: Alfonso given: Zeni - affiliation: University of California, Los Angeles affiliationID: '16569' affiliationSlug: university-of-california-los-angeles-5eED authorID: '31602369' authorName: John K. Fraser authorSequenceNumber: 8 authorSlug: john-k-fraser-5e9ygp family: Fraser given: John K. - affiliation: University of California, Los Angeles affiliationID: '16569' affiliationSlug: university-of-california-los-angeles-5eED authorID: '205945766' authorName: Prosper Benhaim authorSequenceNumber: 9 authorSlug: prosper-benhaim-xXw4r4g family: Benhaim given: Prosper - affiliation: University of California, Los Angeles affiliationID: '16569' affiliationSlug: university-of-california-los-angeles-5eED authorID: '8997341' authorName: Marc H. Hedrick authorSequenceNumber: 10 authorSlug: marc-h-hedrick-XekLkx family: Hedrick given: Marc H. doi: 10.1091/mbc.e02-02-0105 editorialNotices: [] id: 90224106 issns: - 1059-1524 - 1939-4586 issue: '12' journal: Molecular Biology of the Cell journalSlug: 3naW2 memberId: 1076 normalizedTypes: - article page: 4279-4295 preprintLinks: [] publicationLinks: [] publisher: American Society for Cell Biology (ASCB) retracted: false shortJournal: MBoC slug: human-adipose-tissue-is-a-zgLwX8 title: Human Adipose Tissue Is a Source of Multipotent Stem Cells type: journal-article volume: '13' year: 2002 10.1093/bioinformatics/btp101: abstract: >- Summary: We have developed ClueGO, an easy to use Cytoscape plug-in that strongly improves biological interpretation of large lists of genes. ClueGO integrates Gene Ontology (GO) terms as well as KEGG/BioCarta pathways and creates a functionally organized GO/pathway term network. It can analyze one or compare two lists of genes and comprehensively visualizes functionally grouped terms. A one-click update option allows ClueGO to automatically download the most recent GO/KEGG release at any time. ClueGO provides an intuitive representation of the analysis results and can be optionally used in conjunction with the GOlorize plug-in.Availability: http://www.ici.upmc.fr/cluego/cluegoDownload.shtmlContact: jerome.galon@crc.jussieu.frSupplementary information: Supplementary data are available at Bioinformatics online. authors: - affiliation: Inserm affiliationID: '6896' affiliationSlug: inserm-MaEp authorID: '190599640' authorName: Gabriela-Luana Bindea authorSequenceNumber: 1 authorSlug: gabriela-luana-bindea-Le9NdZ5 family: Bindea given: Gabriela-Luana - affiliation: Sorbonne University affiliationID: '21314' affiliationSlug: sorbonne-university-g0bQ authorID: '5929588' authorName: Bernhard Mlecnik authorSequenceNumber: 2 authorSlug: bernhard-mlecnik-3nEwDg family: Mlecnik given: Bernhard - affiliation: Sorbonne University affiliationID: '21314' affiliationSlug: sorbonne-university-g0bQ authorID: '175923479' authorName: Bernhard Mlecnik authorSequenceNumber: 2 authorSlug: bernhard-mlecnik-K6WDab5 family: Mlecnik given: Bernhard - affiliation: Sorbonne University affiliationID: '21314' affiliationSlug: sorbonne-university-g0bQ authorID: '6807462' authorName: Hubert Hackl authorSequenceNumber: 3 authorSlug: hubert-hackl-dvnP03 family: Hackl given: Hubert - affiliation: Sorbonne University affiliationID: '21314' affiliationSlug: sorbonne-university-g0bQ authorID: '5188329' authorName: Pornpimol Charoentong authorSequenceNumber: 4 authorSlug: pornpimol-charoentong-r6X5bA family: Charoentong given: Pornpimol - affiliation: Sorbonne University affiliationID: '21314' affiliationSlug: sorbonne-university-g0bQ authorID: '67195293' authorName: Marie Tosolini authorSequenceNumber: 5 authorSlug: marie-tosolini-Aaz0jE family: Tosolini given: Marie - affiliation: Sorbonne University affiliationID: '21314' affiliationSlug: sorbonne-university-g0bQ authorID: '7006357' authorName: Amos Kirilovsky authorSequenceNumber: 6 authorSlug: amos-kirilovsky-G3MnGK family: Kirilovsky given: Amos - affiliation: Sorbonne University affiliationID: '21314' affiliationSlug: sorbonne-university-g0bQ authorID: '7234686' authorName: Wolf H. Fridman authorSequenceNumber: 7 authorSlug: wolf-h-fridman-4LnnnV family: Fridman given: Wolf H. - affiliation: Sorbonne University affiliationID: '21314' affiliationSlug: sorbonne-university-g0bQ authorID: '191883796' authorName: Franck Pagès authorSequenceNumber: 8 authorSlug: franck-pages-MVy0Lbm family: Pagès given: Franck - affiliation: Sorbonne University affiliationID: '21314' affiliationSlug: sorbonne-university-g0bQ authorID: '51866335' authorName: Zlatko Trajanoski authorSequenceNumber: 9 authorSlug: zlatko-trajanoski-Kvx09e family: Trajanoski given: Zlatko - affiliation: Sorbonne University affiliationID: '21314' affiliationSlug: sorbonne-university-g0bQ authorID: '23365565' authorName: Jérôme Galon authorSequenceNumber: 10 authorSlug: jerome-galon-8NWDRx family: Galon given: Jérôme doi: 10.1093/bioinformatics/btp101 editorialNotices: [] id: 90562888 issns: - 1460-2059 - 1367-4803 issue: '8' journal: Bioinformatics journalSlug: PQ0m2 keywords: - Applications Note memberId: 286 normalizedTypes: - article page: 1091-1093 preprintLinks: [] publicationLinks: [] publisher: Oxford University Press (OUP) retracted: false slug: cluego-a-cytoscape-plug-in-to-3bzmjd title: >- ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks type: journal-article volume: '25' year: 2009 10.1093/bioinformatics/btp120: abstract: >- Motivation: A new protocol for sequencing the messenger RNA in a cell, known as RNA-Seq, generates millions of short sequence fragments in a single run. These fragments, or ‘reads’, can be used to measure levels of gene expression and to identify novel splice variants of genes. However, current software for aligning RNA-Seq data to a genome relies on known splice junctions and cannot identify novel ones. TopHat is an efficient read-mapping algorithm designed to align reads from an RNA-Seq experiment to a reference genome without relying on known splice sites.Results: We mapped the RNA-Seq reads from a recent mammalian RNA-Seq experiment and recovered more than 72% of the splice junctions reported by the annotation-based software from that study, along with nearly 20 000 previously unreported junctions. The TopHat pipeline is much faster than previous systems, mapping nearly 2.2 million reads per CPU hour, which is sufficient to process an entire RNA-Seq experiment in less than a day on a standard desktop computer. We describe several challenges unique to ab initio splice site discovery from RNA-Seq reads that will require further algorithm development.Availability: TopHat is free, open-source software available from http://tophat.cbcb.umd.eduContact: cole@cs.umd.eduSupplementary information: Supplementary data are available at Bioinformatics online. authors: - affiliation: University of Maryland, College Park affiliationID: '2613' affiliationSlug: university-of-maryland-college-park-G3YK authorID: '8885272' authorName: Cole Trapnell authorSequenceNumber: 1 authorSlug: cole-trapnell-wb9XKL family: Trapnell given: Cole - affiliation: University of Maryland, College Park affiliationID: '2613' affiliationSlug: university-of-maryland-college-park-G3YK authorID: '8878157' authorName: Lior Pachter authorSequenceNumber: 2 authorSlug: lior-pachter-G5yZdA family: Pachter given: Lior - affiliation: University of Maryland, College Park affiliationID: '2613' affiliationSlug: university-of-maryland-college-park-G3YK authorID: '483606902' authorName: Steven L. Salzberg authorSequenceNumber: 3 authorSlug: steven-l-salzberg-9bPOnP9 family: Salzberg given: Steven L. doi: 10.1093/bioinformatics/btp120 editorialNotices: [] id: 90562907 issns: - 1460-2059 - 1367-4803 issue: '9' journal: Bioinformatics journalSlug: PQ0m2 keywords: - Original Papers memberId: 286 normalizedTypes: - article page: 1105-1111 preprintLinks: [] publicationLinks: [] publisher: Oxford University Press (OUP) retracted: false slug: tophat-discovering-splice-junctions-with-Y5Kj23 title: 'TopHat: discovering splice junctions with RNA-Seq' type: journal-article volume: '25' year: 2009 10.1126/science.1201475: abstract: >- Eosinophils are associated with helminth immunity and allergy, often in conjunction with alternatively activated macrophages (AAMs). Adipose tissue AAMs are necessary to maintain glucose homeostasis and are induced by the cytokine interleukin-4 (IL-4). Here, we show that eosinophils are the major IL-4-expressing cells in white adipose tissues of mice, and, in their absence, AAMs are greatly attenuated. Eosinophils migrate into adipose by an integrin-dependent process and reconstitute AAMs through an IL-4/IL-13-dependent process. Mice on high-fat diet develop increased body fat, impaired glucose tolerance and insulin resistance in the absence of eosinophils, and helminth-induced adipose eosinophilia enhances glucose tolerance. Our results suggest that eosinophils play an unexpected role in metabolic homeostasis through maintenance of adipose AAMs. authors: - affiliation: University of California, San Francisco affiliationID: '12272' affiliationSlug: university-of-california-san-francisco-w1Ry authorID: '14547459' authorName: Davina Wu authorSequenceNumber: 1 authorSlug: davina-wu-b8KyY8 family: Wu given: Davina - affiliation: University of California, San Francisco affiliationID: '12272' affiliationSlug: university-of-california-san-francisco-w1Ry authorID: '6805954' authorName: Ari B. Molofsky authorSequenceNumber: 2 authorSlug: ari-b-molofsky-68mWl6 family: Molofsky given: Ari B. - affiliation: University of California, San Francisco affiliationID: '12272' affiliationSlug: university-of-california-san-francisco-w1Ry authorID: '11178770' authorName: Hong-Erh Liang authorSequenceNumber: 3 authorSlug: hong-erh-liang-R5K3MN family: Liang given: Hong-Erh - affiliation: Stanford University affiliationID: '23761' affiliationSlug: stanford-university-EVVW authorID: '10317769' authorName: Roberto R. Ricardo-Gonzalez authorSequenceNumber: 4 authorSlug: roberto-r-ricardo-gonzalez-5YAR9A family: Ricardo-Gonzalez given: Roberto R. - affiliation: Stanford University affiliationID: '23761' affiliationSlug: stanford-university-EVVW authorID: '9020513' authorName: Hani A. Jouihan authorSequenceNumber: 5 authorSlug: hani-a-jouihan-G5K8YE family: Jouihan given: Hani A. - affiliation: University of California, San Francisco affiliationID: '12272' affiliationSlug: university-of-california-san-francisco-w1Ry authorID: '8379223' authorName: Jennifer K. Bando authorSequenceNumber: 6 authorSlug: jennifer-k-bando-JWZ2vk family: Bando given: Jennifer K. - affiliation: University of California, San Francisco affiliationID: '12272' affiliationSlug: university-of-california-san-francisco-w1Ry authorID: '32477922' authorName: Ajay Chawla authorSequenceNumber: 7 authorSlug: ajay-chawla-xpjLMg family: Chawla given: Ajay - affiliation: University of California, San Francisco affiliationID: '12272' affiliationSlug: university-of-california-san-francisco-w1Ry authorID: '6048470' authorName: Richard M. Locksley authorSequenceNumber: 8 authorSlug: richard-m-locksley-RVle83 family: Locksley given: Richard M. doi: 10.1126/science.1201475 editorialNotices: [] id: 103081497 issns: - 0036-8075 - 1095-9203 issue: '6026' journal: Science journalSlug: y8MnG keywords: - Article memberId: 221 normalizedTypes: - article page: 243-247 preprintLinks: [] publicationLinks: [] publisher: American Association for the Advancement of Science (AAAS) retracted: false shortJournal: Science slug: eosinophils-sustain-adipose-alternatively-activated-vMKdvV title: >- Eosinophils Sustain Adipose Alternatively Activated Macrophages Associated with Glucose Homeostasis type: journal-article volume: '332' year: 2011 10.1146/annurev-immunol-031210-101322: abstract: >- The modern rise in obesity and its strong association with insulin resistance and type 2 diabetes have elicited interest in the underlying mechanisms of these pathologies. The discovery that obesity itself results in an inflammatory state in metabolic tissues ushered in a research field that examines the inflammatory mechanisms in obesity. Here, we summarize the unique features of this metabolic inflammatory state, termed metaflammation and defined as low-grade, chronic inflammation orchestrated by metabolic cells in response to excess nutrients and energy. We explore the effects of such inflammation in metabolic tissues including adipose, liver, muscle, pancreas, and brain and its contribution to insulin resistance and metabolic dysfunction. Another area in which many unknowns still exist is the origin or mechanism of initiation of inflammatory signaling in obesity. We discuss signals or triggers to the inflammatory response, including the possibility of endoplasmic reticulum stress as an important contributor to metaflammation. Finally, we examine anti-inflammatory therapies for their potential in the treatment of obesity-related insulin resistance and glucose intolerance. authors: - affiliation: Harvard University affiliationID: '14927' affiliationSlug: harvard-university-NmzP authorID: '16265116' authorName: Margaret F. Gregor authorSequenceNumber: 1 authorSlug: margaret-f-gregor-Q6O5K9 family: Gregor given: Margaret F. - affiliation: Harvard University affiliationID: '14927' affiliationSlug: harvard-university-NmzP authorID: '24580538' authorName: Gökhan S. Hotamisligil authorSequenceNumber: 2 authorSlug: gokhan-s-hotamisligil-Vj555z family: Hotamisligil given: Gökhan S. doi: 10.1146/annurev-immunol-031210-101322 editorialNotices: [] id: 105718425 issns: - 0732-0582 - 1545-3278 issue: '1' journal: Annual Review of Immunology journalSlug: ejgZO keywords: - adiposity - metaflammation - insulin resistance - inflammatory signaling - organelle stress - nutrient signals vi Contents memberId: 22 normalizedTypes: - article page: 415-445 preprintLinks: [] publicationLinks: [] publisher: Annual Reviews retracted: false shortJournal: Annu. Rev. Immunol. slug: inflammatory-mechanisms-in-obesity-55ZYk2 title: Inflammatory Mechanisms in Obesity type: journal-article volume: '29' year: 2011 10.1146/annurev.med.53.082901.104057: abstract: >- I review evidence that leptin is a liporegulatory hormone that controls lipid homeostasis in nonadipose tissues during periods of overnutrition. When adipocytes store excess calories as triacylglycerol (TG), leptin secretion rises so as to prevent accumulation of lipids in nonadipose tissues, which are not adapted for TG storage. Whenever leptin action is lacking, whether through leptin deficiency or leptin resistance, overnutrition causes disease of nonadipose tissues with generalized steatosis, lipotoxicity, and lipoapoptosis. Examples of such disorders of liporegulation include generalized lipodystrophies, mutations of leptin and leptin receptor genes, and diet-induced obesity. Lipotoxicity of pancreatic beta-cells, myocardium, and skeletal muscle leads, respectively, to type 2 diabetes, cardiomyopathy, and insulin resistance. In humans this constellation of abnormalities is referred to as the metabolic syndrome, a major health problem in the United States. When lipids overaccumulate in nonadipose tissues during overnutrition, fatty acids enter deleterious pathways such as ceramide production, which, through increased nitric oxide formation, causes apoptosis of lipid-laden cells, such as beta-cells and cardiomyocytes. Lipoapoptosis can be prevented by caloric restriction, by thiazolidinedione treatment, and by administration of nitric oxide blockers. There is now substantial evidence that complications of human obesity may reflect lipotoxicity similar to that described in rodents. authors: - affiliation: The University of Texas Southwestern Medical Center affiliationID: '3092' affiliationSlug: the-university-of-texas-southwestern-W8Yd authorID: '982324166' authorName: Roger H. Unger authorSequenceNumber: 1 authorSlug: roger-h-unger-xPJRMOw family: Unger given: Roger H. doi: 10.1146/annurev.med.53.082901.104057 editorialNotices: [] id: 105740370 issns: - 0066-4219 - 1545-326X issue: '1' journal: Annual Review of Medicine journalSlug: vJGbV memberId: 22 normalizedTypes: - article page: 319-336 preprintLinks: [] publicationLinks: [] publisher: Annual Reviews retracted: false shortJournal: Annu. Rev. Med. slug: lipotoxic-diseases-RX8EN3 title: Lipotoxic Diseases type: journal-article volume: '53' year: 2002 10.1172/jci15001: abstract: >- Lipodystrophy is a rare disorder that is characterized by selective loss of subcutaneous and visceral fat and is associated with hypertriglyceridemia, hepatomegaly, and disordered glucose metabolism. It has recently been shown that chronic leptin treatment ameliorates these abnormalities. Here we show that chronic leptin treatment improves insulin-stimulated hepatic and peripheral glucose metabolism in severely insulin-resistant lipodystrophic patients. This improvement in insulin action was associated with a marked reduction in hepatic and muscle triglyceride content. These data suggest that leptin may represent an important new therapy to reverse the severe hepatic and muscle insulin resistance and associated hepatic steatosis in patients with lipodystrophy authors: - affiliation: Yale University affiliationID: '8068' affiliationSlug: yale-university-kyQE authorID: '19514059' authorName: Kitt Falk Petersen authorSequenceNumber: 1 authorSlug: kitt-falk-petersen-bM98wW family: Petersen given: Kitt Falk - authorID: '101157744' authorName: Elif A. Oral authorSequenceNumber: 2 authorSlug: elif-a-oral-3wQkPJ family: Oral given: Elif A. - affiliation: Yale University affiliationID: '8068' affiliationSlug: yale-university-kyQE authorID: '148536730' authorName: Sylvie Dufour authorSequenceNumber: 3 authorSlug: sylvie-dufour-pJ9mK3 family: Dufour given: Sylvie - affiliation: Yale University affiliationID: '8068' affiliationSlug: yale-university-kyQE authorID: '1529050' authorName: Douglas E. Befroy authorSequenceNumber: 4 authorSlug: douglas-e-befroy-zW4yx family: Befroy given: Douglas E. - affiliation: Yale University affiliationID: '8068' affiliationSlug: yale-university-kyQE authorID: '24586504' authorName: Charlotte E. Ariyan authorSequenceNumber: 5 authorSlug: charlotte-e-ariyan-Wa5r1N family: Ariyan given: Charlotte E. - affiliation: Yale University affiliationID: '8068' affiliationSlug: yale-university-kyQE authorID: '18585489' authorName: Chunli Yu authorSequenceNumber: 6 authorSlug: chunli-yu-Pv5xk0 family: Yu given: Chunli - affiliation: Yale University affiliationID: '8068' affiliationSlug: yale-university-kyQE authorID: '7080077' authorName: Gary W. Cline authorSequenceNumber: 7 authorSlug: gary-w-cline-n68Dgk family: Cline given: Gary W. - affiliation: Amgen affiliationID: '18955' affiliationSlug: amgen-eAJO authorID: '7128516' authorName: Alex M. DePaoli authorSequenceNumber: 8 authorSlug: alex-m-depaoli-QeZ4m9 family: DePaoli given: Alex M. - affiliation: National Institutes of Health affiliationID: '26753' affiliationSlug: national-institutes-of-health-vVaJ authorID: '19599942' authorName: Simeon I. Taylor authorSequenceNumber: 9 authorSlug: simeon-i-taylor-4x3Zj3 family: Taylor given: Simeon I. - affiliation: National Institutes of Health affiliationID: '26753' affiliationSlug: national-institutes-of-health-vVaJ authorID: '7701276' authorName: Phillip Gorden authorSequenceNumber: 10 authorSlug: phillip-gorden-2WWaKL family: Gorden given: Phillip - affiliation: Yale University affiliationID: '8068' affiliationSlug: yale-university-kyQE authorID: '5886223' authorName: Gerald I. Shulman authorSequenceNumber: 11 authorSlug: gerald-i-shulman-J1LvKY family: Shulman given: Gerald I. doi: 10.1172/jci15001 editorialNotices: [] id: 108000450 issns: - 0021-9738 issue: '10' journal: Journal of Clinical Investigation journalSlug: G3Dlb keywords: [] memberId: 232 normalizedTypes: - article page: 1345-1350 preprintLinks: [] publicationLinks: [] publisher: American Society for Clinical Investigation shortJournal: J. Clin. Invest. slug: leptin-reverses-insulin-resistance-and-zmylXY title: >- Leptin reverses insulin resistance and hepatic steatosis in patients with severe lipodystrophy type: journal-article volume: '109' year: 2002 10.1172/jci19246: authors: - affiliation: Columbia University affiliationID: '8275' affiliationSlug: columbia-university-Z3Ly authorID: '150108093' authorName: Stuart P. Weisberg authorSequenceNumber: 1 authorSlug: stuart-p-weisberg-AzNDDL family: Weisberg given: Stuart P. - authorID: '106203356' authorName: Daniel McCann authorSequenceNumber: 2 authorSlug: daniel-mccann-0yx39y family: McCann given: Daniel - authorID: '28017296' authorName: Manisha Desai authorSequenceNumber: 3 authorSlug: manisha-desai-MyWNpp family: Desai given: Manisha - authorID: '12962727' authorName: Michael Rosenbaum authorSequenceNumber: 4 authorSlug: michael-rosenbaum-NYAma9 family: Rosenbaum given: Michael - authorID: '1464126' authorName: Rudolph L. Leibel authorSequenceNumber: 5 authorSlug: rudolph-l-leibel-Rm0A9 family: Leibel given: Rudolph L. - authorID: '15926846' authorName: Anthony W. Ferrante authorSequenceNumber: 6 authorSlug: anthony-w-ferrante-9gA91G family: Ferrante given: Anthony W. doi: 10.1172/jci19246 editorialNotices: [] id: 108001285 issns: - 0021-9738 issue: '12' journal: Journal of Clinical Investigation journalSlug: G3Dlb memberId: 232 normalizedTypes: - article page: 1796-1808 preprintLinks: [] publicationLinks: [] publisher: American Society for Clinical Investigation shortJournal: J. Clin. Invest. slug: obesity-is-associated-with-macrophage-Xm896A title: >- Obesity is associated with macrophage accumulation in adipose tissue type: journal-article volume: '112' year: 2003 10.1172/jci31021: abstract: >- Excess caloric intake can lead to insulin resistance. The underlying reasons are complex but likely related to ectopic lipid deposition in nonadipose tissue. We hypothesized that the inability to appropriately expand subcutaneous adipose tissue may be an underlying reason for insulin resistance and beta cell failure. Mice lacking leptin while overexpressing adiponectin showed normalized glucose and insulin levels and dramatically improved glucose as well as positively affected serum triglyceride levels. Therefore, modestly increasing the levels of circulating full-length adiponectin completely rescued the diabetic phenotype in ob/ob mice. They displayed increased expression of PPARgamma target genes and a reduction in macrophage infiltration in adipose tissue and systemic inflammation. As a result, the transgenic mice were morbidly obese, with significantly higher levels of adipose tissue than their ob/ob littermates, leading to an interesting dichotomy of increased fat mass associated with improvement in insulin sensitivity. Based on these data, we propose that adiponectin acts as a peripheral "starvation" signal promoting the storage of triglycerides preferentially in adipose tissue. As a consequence, reduced triglyceride levels in the liver and muscle convey improved systemic insulin sensitivity. These mice therefore represent what we believe is a novel model of morbid obesity associated with an improved metabolic profile. authors: - affiliation: Yeshiva University affiliationID: '25469' affiliationSlug: yeshiva-university-5QJW authorID: '56710517' authorName: Ja Young Kim authorSequenceNumber: 1 authorSlug: ja-young-kim-EAkxZK family: Kim given: Ja Young - affiliation: Yeshiva University affiliationID: '25469' affiliationSlug: yeshiva-university-5QJW authorID: '74763281' authorName: Esther Van De Wall authorSequenceNumber: 2 authorSlug: esther-van-de-wall-je4JVl family: Wall given: Esther Van De - affiliation: Université Laval affiliationID: '7104' affiliationSlug: universite-laval-WxWg authorID: '73675717' authorName: Mathieu Laplante authorSequenceNumber: 3 authorSlug: mathieu-laplante-E0XDXk family: Laplante given: Mathieu - affiliation: Yeshiva University affiliationID: '25469' affiliationSlug: yeshiva-university-5QJW authorID: '66287203' authorName: Anthony Azzara authorSequenceNumber: 4 authorSlug: anthony-azzara-1daWXj family: Azzara given: Anthony - affiliation: Yeshiva University affiliationID: '25469' affiliationSlug: yeshiva-university-5QJW authorID: '16587171' authorName: Maria E. Trujillo authorSequenceNumber: 5 authorSlug: maria-e-trujillo-Nnvzpm family: Trujillo given: Maria E. - affiliation: University of Cincinnati affiliationID: '19659' affiliationSlug: university-of-cincinnati-bQ3Z authorID: '19153644' authorName: Susanna M. Hofmann authorSequenceNumber: 6 authorSlug: susanna-m-hofmann-3NK93K family: Hofmann given: Susanna M. - affiliation: Yeshiva University affiliationID: '25469' affiliationSlug: yeshiva-university-5QJW authorID: '39422588' authorName: Todd Schraw authorSequenceNumber: 7 authorSlug: todd-schraw-3vkYP2 family: Schraw given: Todd - affiliation: Yeshiva University affiliationID: '25469' affiliationSlug: yeshiva-university-5QJW authorID: '12833947' authorName: Jorge L. Durand authorSequenceNumber: 8 authorSlug: jorge-l-durand-1nNL1y family: Durand given: Jorge L. - affiliation: Yeshiva University affiliationID: '25469' affiliationSlug: yeshiva-university-5QJW authorID: '27704089' authorName: Hua Li authorSequenceNumber: 9 authorSlug: hua-li-PxKg5K family: Li given: Hua - affiliation: Yeshiva University affiliationID: '25469' affiliationSlug: yeshiva-university-5QJW authorID: '17474293' authorName: Guangyu Li authorSequenceNumber: 10 authorSlug: guangyu-li-AxeOP3 family: Li given: Guangyu - affiliation: Yeshiva University affiliationID: '25469' affiliationSlug: yeshiva-university-5QJW authorID: '379055' authorName: Linda A. Jelicks authorSequenceNumber: 11 authorSlug: linda-a-jelicks-eDzJ0 family: Jelicks given: Linda A. - affiliation: Yeshiva University affiliationID: '25469' affiliationSlug: yeshiva-university-5QJW authorID: '17417115' authorName: Mark F. Mehler authorSequenceNumber: 12 authorSlug: mark-f-mehler-bjgA1p family: Mehler given: Mark F. - affiliation: University of Cincinnati affiliationID: '19659' affiliationSlug: university-of-cincinnati-bQ3Z authorID: '424319808' authorName: David Y. Hui authorSequenceNumber: 13 authorSlug: david-y-hui-M2LQQWY family: Hui given: David Y. - affiliation: Université Laval affiliationID: '7104' affiliationSlug: universite-laval-WxWg authorID: '918119' authorName: Yves Deshaies authorSequenceNumber: 14 authorSlug: yves-deshaies-DJkJW family: Deshaies given: Yves - affiliation: Yale University affiliationID: '8068' affiliationSlug: yale-university-kyQE authorID: '5886223' authorName: Gerald I. Shulman authorSequenceNumber: 15 authorSlug: gerald-i-shulman-J1LvKY family: Shulman given: Gerald I. - affiliation: Yeshiva University affiliationID: '25469' affiliationSlug: yeshiva-university-5QJW authorID: '21123336' authorName: Gary J. Schwartz authorSequenceNumber: 16 authorSlug: gary-j-schwartz-l62eza family: Schwartz given: Gary J. - authorID: '52493527' authorName: Philipp E. Scherer authorSequenceNumber: 17 authorSlug: philipp-e-scherer-NOE2vz family: Scherer given: Philipp E. doi: 10.1172/jci31021 editorialNotices: [] id: 108005431 issns: - 0021-9738 issue: '9' journal: Journal of Clinical Investigation journalSlug: G3Dlb keywords: [] memberId: 232 normalizedTypes: - article page: 2621-2637 preprintLinks: [] publicationLinks: [] publisher: American Society for Clinical Investigation retracted: false shortJournal: J. Clin. Invest. slug: obesity-associated-improvements-in-metabolic-profile-ZzJPZP title: >- Obesity-associated improvements in metabolic profile through expansion of adipose tissue type: journal-article volume: '117' year: 2007 10.1172/jci7901: authors: - affiliation: National Institutes of Health affiliationID: '26753' affiliationSlug: national-institutes-of-health-vVaJ authorID: '17567133' authorName: Oksana Gavrilova authorSequenceNumber: 1 authorSlug: oksana-gavrilova-nz5X46 family: Gavrilova given: Oksana - authorID: '7000847' authorName: Bernice Marcus-Samuels authorSequenceNumber: 2 authorSlug: bernice-marcus-samuels-1ZkzDW family: Marcus-Samuels given: Bernice - authorID: '170545366' authorName: David Graham authorSequenceNumber: 3 authorSlug: david-graham-xXXKR6Q family: Graham given: David - authorID: '15023009' authorName: Jason K. Kim authorSequenceNumber: 4 authorSlug: jason-k-kim-vdg5aJ family: Kim given: Jason K. - authorID: '5886223' authorName: Gerald I. Shulman authorSequenceNumber: 5 authorSlug: gerald-i-shulman-J1LvKY family: Shulman given: Gerald I. - authorID: '98232358' authorName: Arthur L. Castle authorSequenceNumber: 6 authorSlug: arthur-l-castle-gJYREJ family: Castle given: Arthur L. - authorID: '8852758' authorName: Charles Vinson authorSequenceNumber: 7 authorSlug: charles-vinson-g1vW31 family: Vinson given: Charles - authorID: '78461932' authorName: Michael Eckhaus authorSequenceNumber: 8 authorSlug: michael-eckhaus-2EKlP1 family: Eckhaus given: Michael - authorID: '6596888' authorName: Marc L. Reitman authorSequenceNumber: 9 authorSlug: marc-l-reitman-3n1GLy family: Reitman given: Marc L. doi: 10.1172/jci7901 editorialNotices: [] id: 108012655 issns: - 0021-9738 issue: '3' journal: Journal of Clinical Investigation journalSlug: G3Dlb memberId: 232 normalizedTypes: - article page: 271-278 preprintLinks: [] publicationLinks: [] publisher: American Society for Clinical Investigation retracted: false shortJournal: J. Clin. Invest. slug: surgical-implantation-of-adipose-tissue-eEOpd6 title: >- Surgical implantation of adipose tissue reverses diabetes in lipoatrophic mice type: journal-article volume: '105' year: 2000 10.1172/jci85664: abstract: >- Increases in eosinophil numbers are associated with infection and allergic diseases, including asthma, but there is also evidence that eosinophils contribute to homeostatic immune processes. In mice, the normal lung contains resident eosinophils (rEos), but their function has not been characterized. Here, we have reported that steady-state pulmonary rEos are IL-5-independent parenchymal Siglec-FintCD62L+CD101lo cells with a ring-shaped nucleus. During house dust mite-induced airway allergy, rEos features remained unchanged, and rEos were accompanied by recruited inflammatory eosinophils (iEos), which were defined as IL-5-dependent peribronchial Siglec-FhiCD62L-CD101hi cells with a segmented nucleus. Gene expression analyses revealed a more regulatory profile for rEos than for iEos, and correspondingly, mice lacking lung rEos showed an increase in Th2 cell responses to inhaled allergens. Such elevation of Th2 responses was linked to the ability of rEos, but not iEos, to inhibit the maturation, and therefore the pro-Th2 function, of allergen-loaded DCs. Finally, we determined that the parenchymal rEos found in nonasthmatic human lungs (Siglec-8+CD62L+IL-3Rlo cells) were phenotypically distinct from the iEos isolated from the sputa of eosinophilic asthmatic patients (Siglec-8+CD62LloIL-3Rhi cells), suggesting that our findings in mice are relevant to humans. In conclusion, our data define lung rEos as a distinct eosinophil subset with key homeostatic functions authors: - affiliation: University of Liège affiliationID: '7680' affiliationSlug: university-of-liege-lQe3 authorID: '177678837' authorName: Claire Mesnil authorSequenceNumber: 1 authorSlug: claire-mesnil-jMXVabV family: Mesnil given: Claire - affiliation: University of Liège affiliationID: '7680' affiliationSlug: university-of-liege-lQe3 authorID: '26329268' authorName: Stéfanie Raulier authorSequenceNumber: 2 authorSlug: stefanie-raulier-kQevag family: Raulier given: Stéfanie - affiliation: University of Liège affiliationID: '7680' affiliationSlug: university-of-liege-lQe3 authorID: '10250781' authorName: Geneviève Paulissen authorSequenceNumber: 3 authorSlug: genevieve-paulissen-j6NRad family: Paulissen given: Geneviève - affiliation: University of Liège affiliationID: '7680' affiliationSlug: university-of-liege-lQe3 authorID: '81340856' authorName: Xue Xiao authorSequenceNumber: 4 authorSlug: xue-xiao-02VJjZ family: Xiao given: Xue - authorID: '214095906' authorName: Mark A. Birrell authorSequenceNumber: 5 authorSlug: mark-a-birrell-zRd19eb family: Birrell given: Mark A. - affiliation: University of Liège affiliationID: '7680' affiliationSlug: university-of-liege-lQe3 authorID: '71959784' authorName: Dimitri Pirottin authorSequenceNumber: 6 authorSlug: dimitri-pirottin-L3lw6X family: Pirottin given: Dimitri - affiliation: University of Liège affiliationID: '7680' affiliationSlug: university-of-liege-lQe3 authorID: '27354415' authorName: Thibaut Janss authorSequenceNumber: 7 authorSlug: thibaut-janss-bNnMW6 family: Janss given: Thibaut - authorID: '11397405' authorName: Philipp Starkl authorSequenceNumber: 8 authorSlug: philipp-starkl-AG3nGv family: Starkl given: Philipp - affiliation: University of Liège affiliationID: '7680' affiliationSlug: university-of-liege-lQe3 authorID: '3244950' authorName: Eve Ramery authorSequenceNumber: 9 authorSlug: eve-ramery-z8zz8 family: Ramery given: Eve - authorID: '8764964' authorName: Monique Henket authorSequenceNumber: 10 authorSlug: monique-henket-yZP256 family: Henket given: Monique - authorID: '33968931' authorName: Florence Schleich authorSequenceNumber: 11 authorSlug: florence-schleich-ZDxvOn family: Schleich given: Florence - affiliation: University of Liège affiliationID: '7680' affiliationSlug: university-of-liege-lQe3 authorID: '11327135' authorName: Marc Radermecker authorSequenceNumber: 12 authorSlug: marc-radermecker-KljyZ5 family: Radermecker given: Marc - authorID: '24111146' authorName: Kris Thielemans authorSequenceNumber: 13 authorSlug: kris-thielemans-9N3bgr family: Thielemans given: Kris - authorID: '25816346' authorName: Laurent Gillet authorSequenceNumber: 14 authorSlug: laurent-gillet-9NYbYN family: Gillet given: Laurent - affiliation: University of Liège affiliationID: '7680' affiliationSlug: university-of-liege-lQe3 authorID: '16452683' authorName: Marc Thiry authorSequenceNumber: 15 authorSlug: marc-thiry-a8kn2r family: Thiry given: Marc - affiliation: University of Liège affiliationID: '7680' affiliationSlug: university-of-liege-lQe3 authorID: '214066975' authorName: Maria G. Belvisi authorSequenceNumber: 16 authorSlug: maria-g-belvisi-ZGb3M0p family: Belvisi given: Maria G. - authorID: '16310778' authorName: Renaud Louis authorSequenceNumber: 17 authorSlug: renaud-louis-Ov2zr8 family: Louis given: Renaud - affiliation: University of Liège affiliationID: '7680' affiliationSlug: university-of-liege-lQe3 authorID: '30627395' authorName: Christophe Desmet authorSequenceNumber: 18 authorSlug: christophe-desmet-YNKLnK family: Desmet given: Christophe - affiliation: University of Liège affiliationID: '7680' affiliationSlug: university-of-liege-lQe3 authorID: '5569771' authorName: Thomas Marichal authorSequenceNumber: 19 authorSlug: thomas-marichal-Nl6Rxz family: Marichal given: Thomas - affiliation: University of Liège affiliationID: '7680' affiliationSlug: university-of-liege-lQe3 authorID: '8267496' authorName: Fabrice Bureau authorSequenceNumber: 20 authorSlug: fabrice-bureau-M2Q2KX family: Bureau given: Fabrice doi: 10.1172/jci85664 editorialNotices: [] id: 108013849 issns: - 0021-9738 - 1558-8238 issue: '9' journal: Journal of Clinical Investigation journalSlug: G3Dlb memberId: 232 normalizedTypes: - article page: 3279-3295 preprintLinks: [] publicationLinks: [] publisher: American Society for Clinical Investigation retracted: false slug: lung-resident-eosinophils-represent-a-distinct-AX0WVZ title: >- Lung-resident eosinophils represent a distinct regulatory eosinophil subset type: journal-article volume: '126' year: 2016 10.1186/s12944-015-0123-1: abstract: >- Insulin resistance is a multi-faceted disruption of the communication between insulin and the interior of a target cell. The underlying cause of insulin resistance appears to be inflammation that can either be increased or decreased by the fatty acid composition of the diet. However, the molecular basis for insulin resistance can be quite different in various organs. This review deals with various types of inflammatory inputs mediated by fatty acids, which affect the extent of insulin resistance in various organs. authors: - authorID: '12372440' authorName: Barry Sears authorSequenceNumber: 1 authorSlug: barry-sears-Lp6ZWm family: Sears given: Barry - authorID: '76675623' authorName: Mary Perry authorSequenceNumber: 2 authorSlug: mary-perry-JPPlnY family: Perry given: Mary doi: 10.1186/s12944-015-0123-1 editorialNotices: [] id: 110076748 issns: - 1476-511X issue: '1' journal: Lipids in Health and Disease journalSlug: Nlkme keywords: - Review memberId: 297 normalizedTypes: - article preprintLinks: [] publicationLinks: [] publisher: Springer Science and Business Media LLC retracted: false shortJournal: Lipids Health Dis slug: the-role-of-fatty-acids-WWJ0Od title: The role of fatty acids in insulin resistance type: journal-article volume: '14' year: 2015 10.1194/jlr.m008771: abstract: >- Storing excess energy for future use during starvation is critical for the survival of mammals. Much of this energy is stored in the form of triacylglycerol (TAG) within lipid droplets, which are present most abundantly in adipocytes and which, in turn, accumulate in depots such as subcutaneous and visceral adipose tissue in mice and humans. TAG in lipid droplets is mobilized during starvation by lipase-catalyzed hydrolysis (lipolysis) to release energy in the forms of glycerol and free fatty acids, providing fuel to other cell types such as muscle and liver. Previous work investigating formation of lipid droplets and regulation of lipolysis has elucidated the importance of lipid dropletassociated proteins for these processes ( 1, 2 ). Based on shared sequence homology, one set of lipid droplet proteins is grouped as the perilipin-adipophilin-tail interacting protein 47 (PAT/TIP47) family of proteins ( 3 ). PAT-related proteins are functionally conserved from mammals to lower organisms such as Drosophila and Dictyostelium spp ( 4 ). In Drosophila , two PAT domain proteins are encoded by the Lsdp1 and Lsd2 genes. Drosophila loss-of-function Lsd2 mutants are lean, whereas Lsd2 overexpression causes obesity ( 5 ). In mammals, PAT proteins can be divided into exchangeable TAG-associated PAT proteins (EPATs) or constitutively TAG-associated PAT proteins (CPATs). EPATs include the TIP47/perilipin-3 (PLIN3), S3-12/PLIN4, and Abstract The lipid droplet-associated fat specifi c protein 27 (FSP27) suppresses lipolysis and thereby enhances triglyceride accumulation in adipocytes. We and others have recently found FSP27 to be a remarkably short-lived protein (half-life, 15 min) due to its rapid ubiquitination and proteasomal degradation. Thus, we tested the hypothesis that lipolytic agents such as tumor necrosis factor-␣ (TNF-␣ ) and isoproterenol modulate FSP27 levels to regulate FFA release. Consistent with this concept, we showed that the lipolytic actions of TNF-␣ , interleukin-1 ␤ (IL-1 ␤ ), and IFN-␥ are accompanied by marked decreases in FSP27 expression and lipid droplet size in mouse adipocytes. Similar depletion of FSP27 using short interfering RNA (siRNA) mimicked the lipolysis-enhancing effect of TNF-␣ , while maintaining stable FSP27 levels using expression of hemagglutinin epitopetagged FSP27 blocked TNF-␣ -mediated lipolysis. In contrast, we show the robust lipolytic action of isoproterenol is paradoxically associated with increases in FSP27 levels and a delayed degradation rate corresponding to decreased ubiquitination. This catecholamine-mediated increase in FSP27 abundance, probably a feedback mechanism for restraining excessive lipolysis by catecholamines, is mimicked by forskolin or 8-bromo-cAMP treatment and is prevented by the protein kinase A (PKA) inhibitor KT5720 or by PKA depletion using siRNA. Taken together, these data identify the regulation of FSP27 as an important intermediate in the mechanism of lipolysis in adipocytes in response to TNF-␣ and isoproterenol. -Ranjit, S authors: - affiliation: University of Massachusetts Medical School affiliationID: '260' affiliationSlug: university-of-massachusetts-medical-school-Qkx authorID: '14107537' authorName: Srijana Ranjit authorSequenceNumber: 1 authorSlug: srijana-ranjit-jX534y family: Ranjit given: Srijana - affiliation: University of Massachusetts Medical School affiliationID: '260' affiliationSlug: university-of-massachusetts-medical-school-Qkx authorID: '9832653' authorName: Emilie Boutet authorSequenceNumber: 2 authorSlug: emilie-boutet-vyMG23 family: Boutet given: Emilie - affiliation: University of Massachusetts Medical School affiliationID: '260' affiliationSlug: university-of-massachusetts-medical-school-Qkx authorID: '16649396' authorName: Pallavi Gandhi authorSequenceNumber: 3 authorSlug: pallavi-gandhi-MlPPNm family: Gandhi given: Pallavi - affiliation: University of Massachusetts Medical School affiliationID: '260' affiliationSlug: university-of-massachusetts-medical-school-Qkx authorID: '102839282' authorName: Matthieu Prot authorSequenceNumber: 4 authorSlug: matthieu-prot-Vr6vGE family: Prot given: Matthieu - affiliation: Kobe University affiliationID: '18337' affiliationSlug: kobe-university-jjG5 authorID: '9831292' authorName: Yoshikazu Tamori authorSequenceNumber: 5 authorSlug: yoshikazu-tamori-WGr3ag family: Tamori given: Yoshikazu - affiliation: University of Massachusetts Medical School affiliationID: '260' affiliationSlug: university-of-massachusetts-medical-school-Qkx authorID: '13735848' authorName: Anil Chawla authorSequenceNumber: 6 authorSlug: anil-chawla-WxWA2J family: Chawla given: Anil - affiliation: Tufts University affiliationID: '10923' affiliationSlug: tufts-university-JlXG authorID: '9750173' authorName: Andrew S. Greenberg authorSequenceNumber: 7 authorSlug: andrew-s-greenberg-rxMPjw family: Greenberg given: Andrew S. - affiliation: Boston University affiliationID: '7891' affiliationSlug: boston-university-11nj authorID: '73159816' authorName: Vishwajeet Puri authorSequenceNumber: 8 authorSlug: vishwajeet-puri-QAp2r6 family: Puri given: Vishwajeet - affiliation: University of Massachusetts Medical School affiliationID: '260' affiliationSlug: university-of-massachusetts-medical-school-Qkx authorID: '8333398' authorName: Michael P. Czech authorSequenceNumber: 9 authorSlug: michael-p-czech-6M0PQ1 family: Czech given: Michael P. doi: 10.1194/jlr.m008771 editorialNotices: [] id: 110258347 issns: - 0022-2275 issue: '2' journal: Journal of Lipid Research journalSlug: y8j1x memberId: 78 normalizedTypes: - article page: 221-236 preprintLinks: [] publicationLinks: [] publisher: Elsevier BV retracted: false shortJournal: Journal of Lipid Research slug: regulation-of-fat-specific-protein-1LNjy6 title: >- Regulation of fat specific protein 27 by isoproterenol and TNF-α to control lipolysis in murine adipocytes type: journal-article volume: '52' year: 2011 10.1194/jlr.m800132-jlr200: abstract: >- Chronic inflammation of adipose tissue in obesity is by now an established phenomenon, but the initiating event(s) of the inflammatory cascade are still unknown. We hypothesized that neutrophil infiltration into adipose tissue may precede macrophage infiltration as in classical immune responses. Here we demonstrate that early (3 and 7 days) after initiating high-fat feeding of C57BL/6J mice, neutrophils transiently infiltrate the parenchyma of intra-abdominal adipose tissue. Mean periepdidymal fat myeloperoxidase expression (representing neutrophils) was significantly increased 3.5-fold (P , 0.01) and 2.9-fold (P , 0.03), at days 3 and 7 compared with day 0. Immunohystochemistry analysis demonstrated a physical binding between neutrophils and adipocytes, which was supported by in vitro adherence assay: mouse peritoneal neutrophils adhered to a monolayer of 3T3-L1 mouse adipocytes, in a manner dependent on their activation state, 41.9 6 3.7% or 29.5 6 2%, by PMA or the IL-8 analog CXCL1 (KC), respectively, compared with 24.8 6 1.5% in unstimulated neutrophils, respectively. The degree of surface exposure of CD11b (Mac-1) corresponded to the percentage of adhered neutrophils. The adherence was prevented by preincubating neutrophils or adipocytes with anti-CD11b or anti-ICAM-1 antibodies. Furthermore, immunoprecipitation of CD11b from lysates of a mixed neutrophil-adipocyte cell population resulted in coimmunoprecipitation of ICAM-1, indicating that the interaction is mediated by neutrophil CD11b and adipocyte ICAM-1.-Elgazar-Carmon, V., A. Rudich, N. Hadad, and R. Levy. Neutrophils transiently infiltrate intra-abdominal fat early in the course of high-fat feeding. authors: - affiliation: Ben-Gurion University of the Negev affiliationID: '22717' affiliationSlug: ben-gurion-university-of-the-negev-ENx1 authorID: '1070938' authorName: Vered Elgazar-Carmon authorSequenceNumber: 1 authorSlug: vered-elgazar-carmon-VewxR family: Elgazar-Carmon given: Vered - affiliation: Ben-Gurion University of the Negev affiliationID: '22717' affiliationSlug: ben-gurion-university-of-the-negev-ENx1 authorID: '5757299' authorName: Assaf Rudich authorSequenceNumber: 2 authorSlug: assaf-rudich-ejmwOr family: Rudich given: Assaf - affiliation: Ben-Gurion University of the Negev affiliationID: '22717' affiliationSlug: ben-gurion-university-of-the-negev-ENx1 authorID: '47105233' authorName: Nurit Hadad authorSequenceNumber: 3 authorSlug: nurit-hadad-nL9AXn family: Hadad given: Nurit - affiliation: Ben-Gurion University of the Negev affiliationID: '22717' affiliationSlug: ben-gurion-university-of-the-negev-ENx1 authorID: '56245434' authorName: Rachel Levy authorSequenceNumber: 4 authorSlug: rachel-levy-O2xWKO family: Levy given: Rachel doi: 10.1194/jlr.m800132-jlr200 editorialNotices: [] id: 110260909 issns: - 0022-2275 issue: '9' journal: Journal of Lipid Research journalSlug: y8j1x keywords: - Supplementary key words inflammation - obesity - adipocytes memberId: 78 normalizedTypes: - article page: 1894-1903 preprintLinks: [] publicationLinks: [] publisher: Elsevier BV retracted: false shortJournal: Journal of Lipid Research slug: neutrophils-transiently-infiltrate-intra-abdominal-fat-vOGP4W title: >- Neutrophils transiently infiltrate intra-abdominal fat early in the course of high-fat feeding type: journal-article volume: '49' year: 2008 10.1371/journal.pone.0134089: abstract: >- Immune reactivity plays an important role in obesity-associated metabolic disorders. We investigated immunometabolic phenotype of C57Bl/6 and BALB/c mice, prototypical Th1 and Th2-type strains, fed chow or high-fat diet (HFD) for 24 weeks. In comparison to C57Bl/6 mice, chow-fed BALB/c mice had higher body weight and weight gain, lower glycemia, more pronounced liver steatosis, but less inflammation and collagen deposition in liver. In response to HFD C57Bl/6 mice exhibited higher weight gain, higher glycemia, HbA1c and liver glycogen content, increased amount of visceral adipose tissue (VAT) and number of VAT associated CD3+CXCR3+ T cells, CD11c+ dendritic cells (DCs) and F4/80+ macrophages than BALB/c mice. More numerous CD3+ and CD8+ T lymphocytes, myeloid DCs, proinflammatory macrophages (F4/80+CD11b+CD11+ and F4/80+IL-1β+) and CD11b+Ly6Chigh monocytes and higher levels of proinflammatory IL-6, TNF-α and IFN-γ were present in liver in HFD-fed C57Bl/6 mice compared with diet-matched BALB/c mice. As opposed to C57Bl/6 mice, HFD induced marked liver steatosis and upregulated the hepatic LXRα and PPARγ genes in BALB/c mice. C57Bl/6 mice fed HFD developed liver fibrosis and increased hepatic procollagen and TGF-β mRNA expression, and IL-33, IL-13 and TGF-β levels in liver homogenates, while BALB/c mice fed HFD had scarce collagen deposition in liver. The obtained results suggest inherent immunometabolic differences in C57Bl/6 and BALB/c mice. Moreover, HFD Th1-type mice on high fat diet regimen are more susceptible to adiposity, liver inflammation and fibrosis, while Th2-type mice to liver steatosis, which is associated with differential immune cell composition in metabolic tissues. Strain-dependent differences in immunometabolic phenotype may be relevant for studies of obesity-associated metabolic diseases in humans. authors: - affiliation: University of Kragujevac affiliationID: '22460' affiliationSlug: university-of-kragujevac-QWPM authorID: '11814723' authorName: Nemanja Jovicic authorSequenceNumber: 1 authorSlug: nemanja-jovicic-Ja34XE family: Jovicic given: Nemanja - affiliation: University of Kragujevac affiliationID: '22460' affiliationSlug: university-of-kragujevac-QWPM authorID: '11217656' authorName: Ilija Jeftic authorSequenceNumber: 2 authorSlug: ilija-jeftic-0a6VzP family: Jeftic given: Ilija - affiliation: University of Kragujevac affiliationID: '22460' affiliationSlug: university-of-kragujevac-QWPM authorID: '8132872' authorName: Ivan Jovanovic authorSequenceNumber: 3 authorSlug: ivan-jovanovic-wb0zdL family: Jovanovic given: Ivan - affiliation: University of Kragujevac affiliationID: '22460' affiliationSlug: university-of-kragujevac-QWPM authorID: '81803378' authorName: Ivan Jovanović authorSequenceNumber: 3 authorSlug: ivan-jovanovic-OeRb04 family: Jovanović given: Ivan - affiliation: University of Kragujevac affiliationID: '22460' affiliationSlug: university-of-kragujevac-QWPM authorID: '7345090' authorName: Gordana Radosavljevic authorSequenceNumber: 4 authorSlug: gordana-radosavljevic-9O90P2 family: Radosavljevic given: Gordana - affiliation: University of Kragujevac affiliationID: '22460' affiliationSlug: university-of-kragujevac-QWPM authorID: '7855593' authorName: Nebojsa Arsenijevic authorSequenceNumber: 5 authorSlug: nebojsa-arsenijevic-ANxZXZ family: Arsenijevic given: Nebojsa - affiliation: University of Kragujevac affiliationID: '22460' affiliationSlug: university-of-kragujevac-QWPM authorID: '6059854' authorName: Miodrag L. Lukic authorSequenceNumber: 6 authorSlug: miodrag-l-lukic-685gnX family: Lukic given: Miodrag L. - affiliation: University of Kragujevac affiliationID: '22460' affiliationSlug: university-of-kragujevac-QWPM authorID: '7904963' authorName: Nada Pejnovic authorSequenceNumber: 7 authorSlug: nada-pejnovic-DxmP2p family: Pejnovic given: Nada doi: 10.1371/journal.pone.0134089 editorialNotices: [] id: 114840636 issns: - 1932-6203 issue: '7' journal: Plos One journalSlug: lZbEk keywords: - Research Article memberId: 340 normalizedTypes: - article page: e0134089 preprintLinks: [] publicationLinks: [] publisher: Public Library of Science (PLoS) retracted: false shortJournal: PLoS ONE slug: differential-immunometabolic-phenotype-in-th1-lJkWKb title: >- Differential Immunometabolic Phenotype in Th1 and Th2 Dominant Mouse Strains in Response to High-Fat Feeding type: journal-article volume: '10' year: 2015 10.1530/joe-16-0229: abstract: >- Group 2 innate lymphoid cells (ILC2s) in white adipose tissue (WAT) promotes WAT browning and assists in preventing the development of obesity. However, how ILC2 in adipose tissue is regulated remains largely unknown. Here, our present study shows that ILC2s are present in brown adipose tissue (BAT) as well as subcutaneous and epididymal WAT (sWAT and eWAT). The fractions of ILC2s, Natural Killer T (NKT) cells and eosinophils in sWAT, eWAT and BAT are significantly decreased by high fat diet (HFD) feeding and leptin deficiency-induced obesity. Consistent with this, the adipose expression and circulating levels of IL-33, a key inducing cytokine of ILC2 are significantly downregulated by obesity. Furthermore, administration of IL-33 markedly increases the fraction of ILC2 and eosinophil as well as expression of UCP1 and tyrosine hydroxylase (TH), a rate-limiting enzyme in catecholamine biosynthesis, in adipose tissue of HFD-fed mice. On the other hand, cold exposure induces the expression levels of IL-33 and UCP1 and the population of ILC2 and eosinophil in sWAT, and these promoting effects of cold stress are reversed by neutralization of IL-33 signaling in vivo. Moreover, the basal and cold-induced IL-33 and ILC2/eosinophil pathways are significantly suppressed by sympathetic denervation via local injection of 6-hydroxydopamine (6-OHDA) in sWAT. Taken together, our data suggests that the ILC2/eosinophil axis in adipose tissue is regulated by sympathetic nervous system and obesity in IL-33-dependent manner, and IL-33-driven ILC2/eosinophil axis are implicated in the development of obesity. authors: - affiliation: Hunan Normal University affiliationID: '14267' affiliationSlug: hunan-normal-university-Jn2G authorID: '20857129' authorName: Xiaofeng Ding authorSequenceNumber: 1 authorSlug: xiaofeng-ding-rQzwdO family: Ding given: Xiaofeng - affiliation: Central South University affiliationID: '26050' affiliationSlug: central-south-university-zdvb authorID: '84945490' authorName: Yan Luo authorSequenceNumber: 2 authorSlug: yan-luo-9k1n5E family: Luo given: Yan - authorID: '103107960' authorName: Xing Zhang authorSequenceNumber: 3 authorSlug: xing-zhang-Qlp0a9 family: Zhang given: Xing - authorID: '61202478' authorName: Handong Zheng authorSequenceNumber: 4 authorSlug: handong-zheng-OdOzp6 family: Zheng given: Handong - authorID: '149529729' authorName: Xin Yang authorSequenceNumber: 5 authorSlug: xin-yang-r55Xv4 family: Yang given: Xin - authorID: '14741551' authorName: Xuexian O. Yang authorSequenceNumber: 6 authorSlug: xuexian-o-yang-YDngGP family: Yang given: Xuexian O. - affiliation: Central South University affiliationID: '26050' affiliationSlug: central-south-university-zdvb authorID: '14791762' authorName: Meilian Liu authorSequenceNumber: 7 authorSlug: meilian-liu-dK4QJG family: Liu given: Meilian doi: 10.1530/joe-16-0229 editorialNotices: [] id: 117609312 issns: - 0022-0795 - 1479-6805 issue: '1' journal: Journal of Endocrinology journalSlug: r6v4w keywords: - Article memberId: 416 normalizedTypes: - article page: 35-48 preprintLinks: [] publicationLinks: [] publisher: Bioscientifica retracted: false slug: il-33-driven-ilc2-eosinophil-axis-in-fat-0Yeywr title: >- IL-33-driven ILC2/eosinophil axis in fat is induced by sympathetic tone and suppressed by obesity type: journal-article volume: '231' year: 2016 result: citations: - refLocation: b13/1 snippet: >- Adipose tissue regulates energy homeostasis through the storage of excess calories and the secretion of adipocyte-derived secretory proteins such as leptin, adiponectin, and resistin 10,11 . However, excessive caloric Published: xx xx xxxx OPEN www.nature.com/scientificreports/ 2 SCIentIfIC REPORTS | (2018) 8:9894 | intake induces the overexpansion of adipocytes, which results in inflammatory responses within adipose tissue 12 .Obesity-related metabolic dysfunctions are associated with an excessive infiltration of immune cells and chronic inflammation in adipose tissue 13,14 .Here, we used eosinophil-deficient ∆dblGATA and wild-type (WT) mice to investigate the roles of eosinophils in obesity, adipose tissue maturation, and associated metabolic responses. We performed whole-genome RNA sequencing of the small intestinal tract, which suggested the presence of a defective lipid metabolism in the absence of eosinophils. source: 10.1038/s41598-018-28371-4 target: 10.1146/annurev-immunol-031210-101322 - refLocation: b14/1 snippet: >- Adipose tissue regulates energy homeostasis through the storage of excess calories and the secretion of adipocyte-derived secretory proteins such as leptin, adiponectin, and resistin 10,11 . However, excessive caloric Published: xx xx xxxx OPEN www.nature.com/scientificreports/ 2 SCIentIfIC REPORTS | (2018) 8:9894 | intake induces the overexpansion of adipocytes, which results in inflammatory responses within adipose tissue 12 .Obesity-related metabolic dysfunctions are associated with an excessive infiltration of immune cells and chronic inflammation in adipose tissue 13,14 .Here, we used eosinophil-deficient ∆dblGATA and wild-type (WT) mice to investigate the roles of eosinophils in obesity, adipose tissue maturation, and associated metabolic responses. We performed whole-genome RNA sequencing of the small intestinal tract, which suggested the presence of a defective lipid metabolism in the absence of eosinophils. source: 10.1038/s41598-018-28371-4 target: 10.1038/nature05483 - refLocation: b13/2 snippet: >- Obesity-related metabolic dysfunctions are associated with an excessive infiltration of immune cells and chronic inflammation in adipose tissue 13,14 . source: 10.1038/s41598-018-28371-4 target: 10.1146/annurev-immunol-031210-101322 - refLocation: b14/2 snippet: >- Obesity-related metabolic dysfunctions are associated with an excessive infiltration of immune cells and chronic inflammation in adipose tissue 13,14 . source: 10.1038/s41598-018-28371-4 target: 10.1038/nature05483 - refLocation: b15/1 snippet: >- S1). Of note, genes associated with lipid metabolism, such as Retnlg, Alox15, and Drd2 [15][16][17] were included in the top 10 downregulated genes (Table S1). Additionally, a GO analysis of the downregulated genes and visualization of a functionally grouped network using the ClueGO plugin 18 suggested a defect in lipase activity (Table S3 and Fig. source: 10.1038/s41598-018-28371-4 target: 10.1038/oby.2009.192 - refLocation: b16/1 snippet: >- S1). Of note, genes associated with lipid metabolism, such as Retnlg, Alox15, and Drd2 [15][16][17] were included in the top 10 downregulated genes (Table S1). Additionally, a GO analysis of the downregulated genes and visualization of a functionally grouped network using the ClueGO plugin 18 suggested a defect in lipase activity (Table S3 and Fig. source: 10.1038/s41598-018-28371-4 target: 10.1006/bmmb.1993.1059 - refLocation: b17/1 snippet: >- S1). Of note, genes associated with lipid metabolism, such as Retnlg, Alox15, and Drd2 [15][16][17] were included in the top 10 downregulated genes (Table S1). Additionally, a GO analysis of the downregulated genes and visualization of a functionally grouped network using the ClueGO plugin 18 suggested a defect in lipase activity (Table S3 and Fig. source: 10.1038/s41598-018-28371-4 target: 10.1007/s00125-005-1735-1 - refLocation: b18/1 snippet: >- Of note, genes associated with lipid metabolism, such as Retnlg, Alox15, and Drd2 [15][16][17] were included in the top 10 downregulated genes (Table S1). Additionally, a GO analysis of the downregulated genes and visualization of a functionally grouped network using the ClueGO plugin 18 suggested a defect in lipase activity (Table S3 and Fig. S2) and a significant decrease in the expression of Lpl was observed ( Fig. source: 10.1038/s41598-018-28371-4 target: 10.1093/bioinformatics/btp101 - refLocation: b10/1 snippet: >- Eosinophil-deficient mice gained less weight and perigonadal fat mass and displayed impaired glucose tolerance on a HFD. Excess caloric intake induces expansion of fat mass and accelerates development of insulin resistance 10 . To further examine the role of eosinophils in adipose tissue expansion and energy homeostasis, we fed 8-10-week-old male WT and ΔdblGATA mice with a HFD for 12 weeks and monitored their body weights weekly. source: 10.1038/s41598-018-28371-4 target: 10.1172/jci31021 - refLocation: b19/1 snippet: >- Eosinophil-deficient mice showed an impaired maturation of perigonadal adipocytes on a HFD. The inability of adipose tissue to expand to accommodate excess calories causes systemic insulin resistance and hyperglycaemia 19 . As we observed an impaired WAT development in HFD-fed ΔdblGATA mice, which showed glucose intolerance, we examined whether eosinophils are required for adipocyte maturation in diet-induced obesity. source: 10.1038/s41598-018-28371-4 target: 10.1172/jci7901 - refLocation: b20/1 snippet: >- Adipocytes support the migration and survival of eosinophils. Since eosinophils are resident cells in the adipose tissue 20 and ΔdblGATA mice showed an impairment of adipocyte maturation, we questioned whether adipocytes support the migration or survival of eosinophils. Eosinophils migrate in a manner dependent on CCL11 and its receptor, CC chemokine receptor (CCR) 3 2,21 . source: 10.1038/s41598-018-28371-4 target: 10.1038/s41598-017-06397-4 - refLocation: b22/1 snippet: >- The perigonadal adipose tissue of eosinophil-deficient mice showed an increased inflammatory response. Excess calorie intake results in chronic inflammation in adipose tissue involving an infiltration of various immune cells [22][23][24][25][26] . In obesity, the infiltrated immune cells promote the production of pro-inflammatory cytokines that inhibit adipogenesis and insulin signalling 27,28 . source: 10.1038/s41598-018-28371-4 target: 10.1172/jci19246 - refLocation: b23/1 snippet: >- The perigonadal adipose tissue of eosinophil-deficient mice showed an increased inflammatory response. Excess calorie intake results in chronic inflammation in adipose tissue involving an infiltration of various immune cells [22][23][24][25][26] . In obesity, the infiltrated immune cells promote the production of pro-inflammatory cytokines that inhibit adipogenesis and insulin signalling 27,28 . source: 10.1038/s41598-018-28371-4 target: 10.1053/j.gastro.2013.04.010 - refLocation: b24/1 snippet: >- The perigonadal adipose tissue of eosinophil-deficient mice showed an increased inflammatory response. Excess calorie intake results in chronic inflammation in adipose tissue involving an infiltration of various immune cells [22][23][24][25][26] . In obesity, the infiltrated immune cells promote the production of pro-inflammatory cytokines that inhibit adipogenesis and insulin signalling 27,28 . source: 10.1038/s41598-018-28371-4 target: 10.1038/nm.1964 - refLocation: b25/1 snippet: >- The perigonadal adipose tissue of eosinophil-deficient mice showed an increased inflammatory response. Excess calorie intake results in chronic inflammation in adipose tissue involving an infiltration of various immune cells [22][23][24][25][26] . In obesity, the infiltrated immune cells promote the production of pro-inflammatory cytokines that inhibit adipogenesis and insulin signalling 27,28 . source: 10.1038/s41598-018-28371-4 target: 10.1038/nm.2353 - refLocation: b26/1 snippet: >- The perigonadal adipose tissue of eosinophil-deficient mice showed an increased inflammatory response. Excess calorie intake results in chronic inflammation in adipose tissue involving an infiltration of various immune cells [22][23][24][25][26] . In obesity, the infiltrated immune cells promote the production of pro-inflammatory cytokines that inhibit adipogenesis and insulin signalling 27,28 . source: 10.1038/s41598-018-28371-4 target: 10.1194/jlr.m800132-jlr200 - refLocation: b27/1 snippet: >- Excess calorie intake results in chronic inflammation in adipose tissue involving an infiltration of various immune cells [22][23][24][25][26] . In obesity, the infiltrated immune cells promote the production of pro-inflammatory cytokines that inhibit adipogenesis and insulin signalling 27,28 . The total numbers of cells isolated from the perigonadal WAT of HFD-fed ΔdblGATA and WT mice were not significantly different (p = 0.1263, data not shown). source: 10.1038/s41598-018-28371-4 target: 10.1074/jbc.m109.061655 - refLocation: b28/1 snippet: >- Excess calorie intake results in chronic inflammation in adipose tissue involving an infiltration of various immune cells [22][23][24][25][26] . In obesity, the infiltrated immune cells promote the production of pro-inflammatory cytokines that inhibit adipogenesis and insulin signalling 27,28 . The total numbers of cells isolated from the perigonadal WAT of HFD-fed ΔdblGATA and WT mice were not significantly different (p = 0.1263, data not shown). source: 10.1038/s41598-018-28371-4 target: 10.1038/ncb942 - refLocation: b29/1 section: The cytokine expression profile in the perigonadal adipose t... snippet: >- Eosinophil-deficient mice showed lipid accumulation in the liver. Excessive lipid accumulation in non-adipose tissues such as the liver, muscle, and pancreas is closely associated with insulin resistance 29 . Given that lipids tend to be stored ectopically in the absence of functional adipocytes 30 , we hypothesized that eosinophil deficiency would influence the development of ectopic fat accumulation. source: 10.1038/s41598-018-28371-4 target: 10.1007/s11892-008-0032-z - refLocation: b30/1 section: The cytokine expression profile in the perigonadal adipose t... snippet: >- Excessive lipid accumulation in non-adipose tissues such as the liver, muscle, and pancreas is closely associated with insulin resistance 29 . Given that lipids tend to be stored ectopically in the absence of functional adipocytes 30 , we hypothesized that eosinophil deficiency would influence the development of ectopic fat accumulation. The livers of HFD-fed ΔdblGATA mice exhibited a paler colour and more prominent lipid deposits than those of WT mice (Fig. source: 10.1038/s41598-018-28371-4 target: 10.1146/annurev.med.53.082901.104057 - refLocation: b31/1 section: Discussion snippet: >- Although eosinophils have been characterized as destructive effector cells that mediate tissue damage during helminth infections and allergic diseases, they are found in various tissues under resting conditions without having obvious pro-inflammatory activities 31,32 . Accumulating evidence has indicated that tissue-resident eosinophils regulate biological processes that are not restricted to Th2 immune responses. source: 10.1038/s41598-018-28371-4 target: 10.1172/jci85664 - refLocation: b32/1 section: Discussion snippet: >- Although eosinophils have been characterized as destructive effector cells that mediate tissue damage during helminth infections and allergic diseases, they are found in various tissues under resting conditions without having obvious pro-inflammatory activities 31,32 . Accumulating evidence has indicated that tissue-resident eosinophils regulate biological processes that are not restricted to Th2 immune responses. source: 10.1038/s41598-018-28371-4 target: 10.1038/mi.2014.123 - refLocation: b33/1 section: Discussion snippet: >- Accumulating evidence has indicated that tissue-resident eosinophils regulate biological processes that are not restricted to Th2 immune responses. Eosinophils in adipose tissue promote the accumulation of alternatively activated macrophages, which protect against insulin resistance induced by obesity-associated changes such as the activation of innate immune activity, alterations in fatty acid uptake, lipogenesis, and energy expenditure that can impact ectopic lipid deposition 33 . Obesity itself does not necessarily induce insulin resistance and primarily results from adipocytes expanding to buffer against excess nutrient uptake 9 . source: 10.1038/s41598-018-28371-4 target: 10.1016/j.cell.2012.02.017 - refLocation: b4/1 section: Discussion snippet: >- These cytokines provide signals that promote the permissive proliferation and differentiation of eosinophils 2,3 . These findings contrast with previous observations that suggested an inverse correlation between the abundance of eosinophils in adipose tissue and adiposity 5,34,35 . The reasons for this difference are unclear, but mouse strains vary in their immunometabolic phenotypes 36 , as evidenced by the difference between BALB/c and C57BL/6 mice in their immune cell profiles with a HFD 37 . source: 10.1038/s41598-018-28371-4 target: 10.1126/science.1201475 - refLocation: b34/1 section: Discussion snippet: >- These cytokines provide signals that promote the permissive proliferation and differentiation of eosinophils 2,3 . These findings contrast with previous observations that suggested an inverse correlation between the abundance of eosinophils in adipose tissue and adiposity 5,34,35 . The reasons for this difference are unclear, but mouse strains vary in their immunometabolic phenotypes 36 , as evidenced by the difference between BALB/c and C57BL/6 mice in their immune cell profiles with a HFD 37 . source: 10.1038/s41598-018-28371-4 target: 10.1016/j.molmet.2017.12.004 - refLocation: b35/1 section: Discussion snippet: >- These cytokines provide signals that promote the permissive proliferation and differentiation of eosinophils 2,3 . These findings contrast with previous observations that suggested an inverse correlation between the abundance of eosinophils in adipose tissue and adiposity 5,34,35 . The reasons for this difference are unclear, but mouse strains vary in their immunometabolic phenotypes 36 , as evidenced by the difference between BALB/c and C57BL/6 mice in their immune cell profiles with a HFD 37 . source: 10.1038/s41598-018-28371-4 target: 10.1530/joe-16-0229 - refLocation: b36/1 section: Discussion snippet: >- These findings contrast with previous observations that suggested an inverse correlation between the abundance of eosinophils in adipose tissue and adiposity 5,34,35 . The reasons for this difference are unclear, but mouse strains vary in their immunometabolic phenotypes 36 , as evidenced by the difference between BALB/c and C57BL/6 mice in their immune cell profiles with a HFD 37 . In line with this, chow diet-fed male C57BL/6 mice showed significantly more eosinophils in the perigonadal adipose tissue than BALB/c mice, while showing fewer eosinophils in the small intestine ( Fig. source: 10.1038/s41598-018-28371-4 target: 10.1007/s00125-013-2846-8 - refLocation: b37/1 section: Discussion snippet: >- These findings contrast with previous observations that suggested an inverse correlation between the abundance of eosinophils in adipose tissue and adiposity 5,34,35 . The reasons for this difference are unclear, but mouse strains vary in their immunometabolic phenotypes 36 , as evidenced by the difference between BALB/c and C57BL/6 mice in their immune cell profiles with a HFD 37 . In line with this, chow diet-fed male C57BL/6 mice showed significantly more eosinophils in the perigonadal adipose tissue than BALB/c mice, while showing fewer eosinophils in the small intestine ( Fig. source: 10.1038/s41598-018-28371-4 target: 10.1371/journal.pone.0134089 - refLocation: b38/1 section: Discussion snippet: >- S13). There are likely differences in microbiota, and thus endotoxin exposure may explain the weight difference between results of previous reports and those of our study, as exposure to microbial endotoxins may alter eosinophil maturation and activities 38 . Considering that our results are consistent with previous reports indicating eosinophils role in the regulation of metabolic homeostasis 4,5,35 , we propose that differences in mice strain and cohort might account for the divergence on eosinophil abundance in the adipose tissue between this study and previous observations. source: 10.1038/s41598-018-28371-4 target: 10.1016/j.celrep.2016.06.007 - refLocation: b3/1 section: Discussion snippet: >- There are likely differences in microbiota, and thus endotoxin exposure may explain the weight difference between results of previous reports and those of our study, as exposure to microbial endotoxins may alter eosinophil maturation and activities 38 . Considering that our results are consistent with previous reports indicating eosinophils role in the regulation of metabolic homeostasis 4,5,35 , we propose that differences in mice strain and cohort might account for the divergence on eosinophil abundance in the adipose tissue between this study and previous observations. source: 10.1038/s41598-018-28371-4 target: 10.1016/j.cell.2014.03.066 - refLocation: b4/2 section: Discussion snippet: >- There are likely differences in microbiota, and thus endotoxin exposure may explain the weight difference between results of previous reports and those of our study, as exposure to microbial endotoxins may alter eosinophil maturation and activities 38 . Considering that our results are consistent with previous reports indicating eosinophils role in the regulation of metabolic homeostasis 4,5,35 , we propose that differences in mice strain and cohort might account for the divergence on eosinophil abundance in the adipose tissue between this study and previous observations. source: 10.1038/s41598-018-28371-4 target: 10.1126/science.1201475 - refLocation: b35/2 section: Discussion snippet: >- There are likely differences in microbiota, and thus endotoxin exposure may explain the weight difference between results of previous reports and those of our study, as exposure to microbial endotoxins may alter eosinophil maturation and activities 38 . Considering that our results are consistent with previous reports indicating eosinophils role in the regulation of metabolic homeostasis 4,5,35 , we propose that differences in mice strain and cohort might account for the divergence on eosinophil abundance in the adipose tissue between this study and previous observations. source: 10.1038/s41598-018-28371-4 target: 10.1530/joe-16-0229 - refLocation: b8/1 section: Discussion snippet: >- The fat cells of adipose tissue are the only cells in the body that are designed to safely contain large amounts of fat 9 . Therefore, the impaired development of perigonadal adipose tissue observed in HFD-fed ΔdblGATA mice may lead to the accumulation of lipid outside adipose tissue. source: 10.1038/s41598-018-28371-4 target: 10.1186/s12944-015-0123-1 - refLocation: b33/2 section: Discussion snippet: >- Therefore, the impaired development of perigonadal adipose tissue observed in HFD-fed ΔdblGATA mice may lead to the accumulation of lipid outside adipose tissue. The excessive accumulation of lipids in non-adipose tissues is closely associated with insulin resistance 33 , and we propose that ectopic fat accumulation in HFD-fed ΔdblGATA mice might account for their glucose intolerance. Although increased visceral adiposity has been implicated in hepatic insulin resistance, patients with severe lipodystrophy, as well as a mouse model of lipoatrophy, manifest insulin resistance associated with lipid deposition in the liver 39,40 . source: 10.1038/s41598-018-28371-4 target: 10.1016/j.cell.2012.02.017 - refLocation: b39/1 section: Discussion snippet: >- The excessive accumulation of lipids in non-adipose tissues is closely associated with insulin resistance 33 , and we propose that ectopic fat accumulation in HFD-fed ΔdblGATA mice might account for their glucose intolerance. Although increased visceral adiposity has been implicated in hepatic insulin resistance, patients with severe lipodystrophy, as well as a mouse model of lipoatrophy, manifest insulin resistance associated with lipid deposition in the liver 39,40 . The significant decrease in the expression of Pparg, which encodes a transcription factor involved in adipocyte differentiation, and genes associated with lipid droplet formation (Cav1, Cav2, Cd36, and Cidec) in the perigonadal WAT of HFD-fed ΔdblGATA mice ( Fig. source: 10.1038/s41598-018-28371-4 target: 10.1172/jci15001 - refLocation: b40/1 section: Discussion snippet: >- The excessive accumulation of lipids in non-adipose tissues is closely associated with insulin resistance 33 , and we propose that ectopic fat accumulation in HFD-fed ΔdblGATA mice might account for their glucose intolerance. Although increased visceral adiposity has been implicated in hepatic insulin resistance, patients with severe lipodystrophy, as well as a mouse model of lipoatrophy, manifest insulin resistance associated with lipid deposition in the liver 39,40 . The significant decrease in the expression of Pparg, which encodes a transcription factor involved in adipocyte differentiation, and genes associated with lipid droplet formation (Cav1, Cav2, Cd36, and Cidec) in the perigonadal WAT of HFD-fed ΔdblGATA mice ( Fig. source: 10.1038/s41598-018-28371-4 target: 10.1074/jbc.275.12.8456 - refLocation: b41/1 section: Discussion snippet: >- 3) suggests insufficient lipid storage in adipose tissue in the absence of eosinophils. Concordantly, the expression of Lpl, Slc2a4, and Adipoq, which are regulated by Pparg and involved in glucose homeostasis 41 , significantly decreased in the perigonadal adipose tissue of HFD-fed ΔdblGATA mice (Fig. 3). source: 10.1038/s41598-018-28371-4 target: 10.1074/jbc.m114.628487 - refLocation: b28/2 section: Discussion snippet: >- We suggest that an altered immune environment in the perigonadal fat of HFD-fed ΔdblGATA accounts for the decreased expression of adipogenic genes. The exposure of preadipocytes to pro-inflammatory cytokines inhibits adipogenesis by reducing the expression of Pparg and inhibiting the adipogenic action of insulin 28 . Th1 cytokines, including IFN-γ, can inhibit insulin signalling and lipid droplet formation 27,42 , while Th2 cytokines, including IL-4 and IL-13, can suppress inflammatory responses in adipose tissue 43 . source: 10.1038/s41598-018-28371-4 target: 10.1038/ncb942 - refLocation: b27/2 section: Discussion snippet: >- The exposure of preadipocytes to pro-inflammatory cytokines inhibits adipogenesis by reducing the expression of Pparg and inhibiting the adipogenic action of insulin 28 . Th1 cytokines, including IFN-γ, can inhibit insulin signalling and lipid droplet formation 27,42 , while Th2 cytokines, including IL-4 and IL-13, can suppress inflammatory responses in adipose tissue 43 . The increased expression of Ifng and decreased expression of Il4 and Il13 in the perigonadal fat of HFD-fed ΔdblGATA mice imply that the microenvironments of the WAT of these mice are unfavourable for adipocyte maturation. source: 10.1038/s41598-018-28371-4 target: 10.1074/jbc.m109.061655 - refLocation: b42/1 section: Discussion snippet: >- The exposure of preadipocytes to pro-inflammatory cytokines inhibits adipogenesis by reducing the expression of Pparg and inhibiting the adipogenic action of insulin 28 . Th1 cytokines, including IFN-γ, can inhibit insulin signalling and lipid droplet formation 27,42 , while Th2 cytokines, including IL-4 and IL-13, can suppress inflammatory responses in adipose tissue 43 . The increased expression of Ifng and decreased expression of Il4 and Il13 in the perigonadal fat of HFD-fed ΔdblGATA mice imply that the microenvironments of the WAT of these mice are unfavourable for adipocyte maturation. source: 10.1038/s41598-018-28371-4 target: 10.1194/jlr.m008771 - refLocation: b43/1 section: Discussion snippet: >- The exposure of preadipocytes to pro-inflammatory cytokines inhibits adipogenesis by reducing the expression of Pparg and inhibiting the adipogenic action of insulin 28 . Th1 cytokines, including IFN-γ, can inhibit insulin signalling and lipid droplet formation 27,42 , while Th2 cytokines, including IL-4 and IL-13, can suppress inflammatory responses in adipose tissue 43 . The increased expression of Ifng and decreased expression of Il4 and Il13 in the perigonadal fat of HFD-fed ΔdblGATA mice imply that the microenvironments of the WAT of these mice are unfavourable for adipocyte maturation. source: 10.1038/s41598-018-28371-4 target: 10.1038/nri2921 - refLocation: b22/2 section: Discussion snippet: >- Obesity is associated with an increased infiltration of macrophages, preferentially the pro-inflammatory M1 phenotype, into adipose tissue 22 , and IL-4 produced by adipose tissue eosinophils supports the polarization of anti-inflammatory M2 macrophages 5 . In agreement this with this idea, conditioned media (CM) collected from eosinophilic cell line EoL-1 cells or CM from palmitic-acid stimulated EoL-1 cells promoted M2-polarization of monocytic THP-1 cells (Fig. source: 10.1038/s41598-018-28371-4 target: 10.1172/jci19246 - refLocation: b4/3 section: Discussion snippet: >- Obesity is associated with an increased infiltration of macrophages, preferentially the pro-inflammatory M1 phenotype, into adipose tissue 22 , and IL-4 produced by adipose tissue eosinophils supports the polarization of anti-inflammatory M2 macrophages 5 . In agreement this with this idea, conditioned media (CM) collected from eosinophilic cell line EoL-1 cells or CM from palmitic-acid stimulated EoL-1 cells promoted M2-polarization of monocytic THP-1 cells (Fig. source: 10.1038/s41598-018-28371-4 target: 10.1126/science.1201475 - refLocation: b44/1 section: Discussion snippet: >- 5). Given that hypoxia induces macrophage proliferation and polarization towards the M2 phenotype 44,45 , it is plausible that hypoxia determined the composition of macrophages in the adipose tissue of HFD-fed ΔdblGATA mice. The significantly elevated concentration of lactate in the perigonadal WAT of HFD-fed ΔdblGATA mice also supports this idea (Fig. source: 10.1038/s41598-018-28371-4 target: 10.1002/ijc.21422 - refLocation: b45/1 section: Discussion snippet: >- 5). Given that hypoxia induces macrophage proliferation and polarization towards the M2 phenotype 44,45 , it is plausible that hypoxia determined the composition of macrophages in the adipose tissue of HFD-fed ΔdblGATA mice. The significantly elevated concentration of lactate in the perigonadal WAT of HFD-fed ΔdblGATA mice also supports this idea (Fig. source: 10.1038/s41598-018-28371-4 target: 10.1080/2162402x.2015.1056442 - refLocation: b46/1 section: Discussion snippet: >- Although adipose tissue is rich in stem cells that can differentiate into fat cells to contain excess energy 46 , the pro-inflammatory microenvironment of adipose tissue induced by obesity is associated with the inhibition of adipocyte maturation and increased adipocyte death 10,12 . Our data demonstrate that adipocytes provide signals to promote eosinophil migration and survival, and that eosinophils support adipocyte maturation and protect adipose tissue against inflammatory changes. source: 10.1038/s41598-018-28371-4 target: 10.1091/mbc.e02-02-0105 - refLocation: b10/2 section: Discussion snippet: >- Although adipose tissue is rich in stem cells that can differentiate into fat cells to contain excess energy 46 , the pro-inflammatory microenvironment of adipose tissue induced by obesity is associated with the inhibition of adipocyte maturation and increased adipocyte death 10,12 . Our data demonstrate that adipocytes provide signals to promote eosinophil migration and survival, and that eosinophils support adipocyte maturation and protect adipose tissue against inflammatory changes. source: 10.1038/s41598-018-28371-4 target: 10.1172/jci31021 - refLocation: b12/1 section: Discussion snippet: >- Although adipose tissue is rich in stem cells that can differentiate into fat cells to contain excess energy 46 , the pro-inflammatory microenvironment of adipose tissue induced by obesity is associated with the inhibition of adipocyte maturation and increased adipocyte death 10,12 . Our data demonstrate that adipocytes provide signals to promote eosinophil migration and survival, and that eosinophils support adipocyte maturation and protect adipose tissue against inflammatory changes. source: 10.1038/s41598-018-28371-4 target: 10.1038/ijo.2008.229 - refLocation: b47/1 section: Method snippet: >- RNA isolated from the small intestine of 8-10-week-old WT (n = 4) and ∆dblGATA mice (n = 4) was subjected to RNA sequencing at the Cincinnati Children's Hospital Medical Center sequencing core. Sequencing data were demultiplexed and reads were mapped to the mm10 mouse genome reference using TopHat 47 . The total number of mapped reads per transcript was determined and the data were normalized to detect the number of fragments per kilobase of exon per million fragments mapped (FPKM) using Cufflinks 48 . source: 10.1038/s41598-018-28371-4 target: 10.1093/bioinformatics/btp120 - refLocation: b48/1 section: Method snippet: >- Sequencing data were demultiplexed and reads were mapped to the mm10 mouse genome reference using TopHat 47 . The total number of mapped reads per transcript was determined and the data were normalized to detect the number of fragments per kilobase of exon per million fragments mapped (FPKM) using Cufflinks 48 . An FPKM >0.1 in at least 1 of the analysed samples was used to filter for potentially significant gene expression. source: 10.1038/s41598-018-28371-4 target: 10.1038/nbt.1621 - refLocation: b50/1 section: Method snippet: >- Insulin (0.75 U/kg) or saline was infused into the liver via the portal vein. Five minutes after infusion, liver, perigonadal fat, and skeletal muscle were quickly excised and snap-frozen in liquid nitrogen 50 . At sacrifice, all mice were weighed and the livers and perigonadal fat were removed and weighed. source: 10.1038/s41598-018-28371-4 target: 10.1002/hep.26015 - refLocation: b50/2 section: Method snippet: >- Total protein extraction and western blot analysis. The tissue lysates were prepared in ice-cold tissue lysis buffer (50 mM Tris-HCl, pH 7.5; 150 mM NaCl; 1% Nonidet P-40; 0.5% sodium deoxycholate; 0.1% SDS) containing 50 mM NaF, 2 mM Na 3 VO 4 , protease inhibitors (Sigma-Aldrich, St. Louis, MO, USA) and phosphatase inhibitors (Sigma-Aldrich) and total protein was extracted as previously described 50 . Samples from tissue lysates were resolved by SDS-PAGE and then transferred to a nitrocellulose membrane. source: 10.1038/s41598-018-28371-4 target: 10.1002/hep.26015 - refLocation: b20/2 section: Isolation of eosinophils. snippet: >- Eosinophils were isolated from the peritoneal cavity of CD3-IL-5 transgenic mice as described 20 and used for chemotaxis assay and co-culture with adipocyte-differentiated 3T3-L1 cells. Total cells were extracted and subjected to lymphocyte depletion using a MACS ® system with antibodies against CD90.2 and CD45R (Miltenyi Biotec, Auburn, CA, USA). source: 10.1038/s41598-018-28371-4 target: 10.1038/s41598-017-06397-4 filetype: pdf metadata: abstract: >- Accumulating data have indicated a fundamental role of eosinophils in regulating adipose tissue homeostasis. Here, we performed whole-genome RNA sequencing of the small intestinal tract, which suggested the presence of impaired lipid metabolism in eosinophil-deficient ΔdblGATA mice. ΔdblGATA mice fed a high-fat diet (HFD) showed reduced body fat mass, impaired enlargement of adipocytes, decreased expression of adipogenic genes, and developed glucose intolerance. HFD induced accumulation of eosinophils in the perigonadal white adipose tissue. Concordantly, adipocytedifferentiated 3T3-L1 cells promoted the migration of eosinophils through the expression of CCL11 (eotaxin-1) and likely promoted their survival through the expression of interleukin (IL)-3, IL-5, and granulocyte-macrophage colony-stimulating factor. HFD-fed ΔdblGATA mice showed increased infiltration of macrophages, CD4 + T-cells, and B-cells, increased expression of interferon-γ, and decreased expression of IL-4 and IL-13 in white adipose tissue. Interferon-γ treatment significantly decreased lipid deposition in adipocyte-differentiated 3T3-L1 cells, while IL-4 treatment promoted lipid accumulation. Notably, HFD-fed ΔdblGATA mice showed increased lipid storage in the liver as compared with wild-type mice. We propose that obesity promotes the infiltration of eosinophils into adipose tissue that subsequently contribute to the metabolic homeostasis by promoting adipocyte maturation.Eosinophils have been considered as destructive cells involved in T helper cell type (Th) 2 immune responses in parasitic infections or allergic diseases 1 . However, accumulating evidence has indicated additional roles for eosinophils. For example, eosinophils reside in several organs including the gastrointestinal tract 2,3 and adipose tissue and contribute to metabolic homeostasis 4,5 . Adipose tissue eosinophils secrete interleukin (IL)-4 and induce the polarization of white adipose tissue (WAT) macrophages into alternatively-activated macrophages, which support glucose tolerance by regulating local catecholamine stores in the microenvironment through the import of catecholamines produced by nerve cells 4,6,7 . Despite recent advances, the roles of eosinophils in the adipose tissue and their effects on adipocyte function remain incompletely understood.Obesity and its associated metabolic disorders are serious health problems worldwide 8 . However, obesity is not necessarily an adverse metabolic condition when the excess fat is stored in adipose tissue that responds to insulin 9 . Adipose tissue regulates energy homeostasis through the storage of excess calories and the secretion of adipocyte-derived secretory proteins such as leptin, adiponectin, and resistin 10,11 . However, excessive caloric Published: xx xx xxxx OPEN www.nature.com/scientificreports/ 2 SCIentIfIC REPORTS | (2018) 8:9894 | intake induces the overexpansion of adipocytes, which results in inflammatory responses within adipose tissue 12 .Obesity-related metabolic dysfunctions are associated with an excessiv... authors: - family: Lee given: Eun-Hui - family: Itan given: Michal - family: Jang given: Jinsun - family: Gu given: Hyeon-Jung - family: Rozenberg given: Perri - family: Mingler given: Melissa - family: Wen given: Ting - family: Yoon given: Jiyoung - family: Park given: Shi-Young - family: Roh given: Joo - family: Choi given: Soo - family: Park given: Woo-Jae - family: Munitz given: Ariel - family: Jung given: Yunjae keywords: [] title: >- Eosinophils support adipocyte maturation and promote glucose tolerance in obesity OPEN source: 10.1038/s41598-018-28371-4 status: SUCCESS tallies: 10.1002/hep.26015: citingPublications: 125 contradicting: 1 doi: 10.1002/hep.26015 mentioning: 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