Adipose tissue invariant NKT cells protect against diet-induced obesity and metabolic disorder through regulatory cytokine production.

Hdl Handle:
http://hdl.handle.net/10147/297471
Title:
Adipose tissue invariant NKT cells protect against diet-induced obesity and metabolic disorder through regulatory cytokine production.
Authors:
Lynch, Lydia; Nowak, Michael; Varghese, Bindu; Clark, Justice; Hogan, Andrew E; Toxavidis, Vasillis; Balk, Steven P; O'Shea, Donal; O'Farrelly, Cliona; Exley, Mark A
Affiliation:
Hematology/Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. llynch1@bidmc.harvard.edu
Citation:
Adipose tissue invariant NKT cells protect against diet-induced obesity and metabolic disorder through regulatory cytokine production. 2012, 37 (3):574-87 Immunity
Publisher:
Immunity
Journal:
Immunity
Issue Date:
21-Sep-2012
URI:
http://hdl.handle.net/10147/297471
DOI:
10.1016/j.immuni.2012.06.016
PubMed ID:
22981538
Abstract:
Invariant natural killer T (iNKT) cells are evolutionarily conserved innate T cells that influence inflammatory responses. We have shown that iNKT cells, previously thought to be rare in humans, were highly enriched in human and murine adipose tissue, and that as adipose tissue expanded in obesity, iNKT cells were depleted, correlating with proinflammatory macrophage infiltration. iNKT cell numbers were restored in mice and humans after weight loss. Mice lacking iNKT cells had enhanced weight gain, larger adipocytes, fatty livers, and insulin resistance on a high-fat diet. Adoptive transfer of iNKT cells into obese mice or in vivo activation of iNKT cells via their lipid ligand, alpha-galactocylceramide, decreased body fat, triglyceride levels, leptin, and fatty liver and improved insulin sensitivity through anti-inflammatory cytokine production by adipose-derived iNKT cells. This finding highlights the potential of iNKT cell-targeted therapies, previously proven to be safe in humans, in the management of obesity and its consequences.
Item Type:
Article
Language:
en
MeSH:
Adipose Tissue; Adoptive Transfer; Adult; Animals; Antigens, CD11c; Antigens, CD1d; Cytokines; Diet, High-Fat; Female; Flow Cytometry; Humans; Liver; Lymphocyte Count; Macrophages; Male; Metabolic Diseases; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Obese; Middle Aged; Natural Killer T-Cells; Obesity; Spleen; Young Adult
ISSN:
1097-4180

Full metadata record

DC FieldValue Language
dc.contributor.authorLynch, Lydiaen_GB
dc.contributor.authorNowak, Michaelen_GB
dc.contributor.authorVarghese, Binduen_GB
dc.contributor.authorClark, Justiceen_GB
dc.contributor.authorHogan, Andrew Een_GB
dc.contributor.authorToxavidis, Vasillisen_GB
dc.contributor.authorBalk, Steven Pen_GB
dc.contributor.authorO'Shea, Donalen_GB
dc.contributor.authorO'Farrelly, Clionaen_GB
dc.contributor.authorExley, Mark Aen_GB
dc.date.accessioned2013-08-07T08:57:00Z-
dc.date.available2013-08-07T08:57:00Z-
dc.date.issued2012-09-21-
dc.identifier.citationAdipose tissue invariant NKT cells protect against diet-induced obesity and metabolic disorder through regulatory cytokine production. 2012, 37 (3):574-87 Immunityen_GB
dc.identifier.issn1097-4180-
dc.identifier.pmid22981538-
dc.identifier.doi10.1016/j.immuni.2012.06.016-
dc.identifier.urihttp://hdl.handle.net/10147/297471-
dc.description.abstractInvariant natural killer T (iNKT) cells are evolutionarily conserved innate T cells that influence inflammatory responses. We have shown that iNKT cells, previously thought to be rare in humans, were highly enriched in human and murine adipose tissue, and that as adipose tissue expanded in obesity, iNKT cells were depleted, correlating with proinflammatory macrophage infiltration. iNKT cell numbers were restored in mice and humans after weight loss. Mice lacking iNKT cells had enhanced weight gain, larger adipocytes, fatty livers, and insulin resistance on a high-fat diet. Adoptive transfer of iNKT cells into obese mice or in vivo activation of iNKT cells via their lipid ligand, alpha-galactocylceramide, decreased body fat, triglyceride levels, leptin, and fatty liver and improved insulin sensitivity through anti-inflammatory cytokine production by adipose-derived iNKT cells. This finding highlights the potential of iNKT cell-targeted therapies, previously proven to be safe in humans, in the management of obesity and its consequences.en_GB
dc.language.isoenen
dc.publisherImmunityen_GB
dc.rightsArchived with thanks to Immunityen_GB
dc.subject.meshAdipose Tissue-
dc.subject.meshAdoptive Transfer-
dc.subject.meshAdult-
dc.subject.meshAnimals-
dc.subject.meshAntigens, CD11c-
dc.subject.meshAntigens, CD1d-
dc.subject.meshCytokines-
dc.subject.meshDiet, High-Fat-
dc.subject.meshFemale-
dc.subject.meshFlow Cytometry-
dc.subject.meshHumans-
dc.subject.meshLiver-
dc.subject.meshLymphocyte Count-
dc.subject.meshMacrophages-
dc.subject.meshMale-
dc.subject.meshMetabolic Diseases-
dc.subject.meshMice-
dc.subject.meshMice, Inbred C57BL-
dc.subject.meshMice, Knockout-
dc.subject.meshMice, Obese-
dc.subject.meshMiddle Aged-
dc.subject.meshNatural Killer T-Cells-
dc.subject.meshObesity-
dc.subject.meshSpleen-
dc.subject.meshYoung Adult-
dc.titleAdipose tissue invariant NKT cells protect against diet-induced obesity and metabolic disorder through regulatory cytokine production.en_GB
dc.typeArticleen
dc.contributor.departmentHematology/Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. llynch1@bidmc.harvard.eduen_GB
dc.identifier.journalImmunityen_GB
dc.description.fundingOtheren
dc.description.provinceLeinsteren
dc.description.peer-reviewpeer-reviewen

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