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Article: Activation of natural killer T cells promotes M2 Macrophage polarization in adipose tissue and improves systemic glucose tolerance via interleukin-4 (IL-4)/STAT6 protein signaling axis in obesity
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TitleActivation of natural killer T cells promotes M2 Macrophage polarization in adipose tissue and improves systemic glucose tolerance via interleukin-4 (IL-4)/STAT6 protein signaling axis in obesity
 
AuthorsJi, Y2
Sun, S2
Xu, A3
Bhargava, P1
Yang, L2
Lam, KSL3
Gao, B5
Lee, CH1
Kersten, S2 4
Qi, L2
 
Issue Date2012
 
PublisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/
 
CitationJournal of Biological Chemistry, 2012, v. 287 n. 17, p. 13561-13571 [How to Cite?]
DOI: http://dx.doi.org/10.1074/jbc.M112.350066
 
AbstractNatural killer T (NKT) cells are important therapeutic targets in various disease models and are under clinical trials for cancer patients. However, their function in obesity and type 2 diabetes remains unclear. Our data show that adipose tissues of both mice and humans contain a population of type 1 NKT cells, whose abundance decreases with increased adiposity and insulin resistance. Although loss-of-function of NKT cells had no effect on glucose tolerance in animals with prolonged high fat diet feeding, activation of NKT cells by lipid agonist alpha-galactosylceramide enhances alternative macrophage polarization in adipose tissue and improves glucose homeostasis in animals at different stages of obesity. Furthermore, the effect of NKT cells is largely mediated by the IL-4/STAT6 signaling axis in obese adipose tissue. Thus, our data identify a novel therapeutic target for the treatment of obesity-associated inflammation and type 2 diabetes.
 
ISSN0021-9258
2012 Impact Factor: 4.651
2012 SCImago Journal Rankings: 2.723
 
DOIhttp://dx.doi.org/10.1074/jbc.M112.350066
 
PubMed Central IDPMC3340139
 
DC FieldValue
dc.contributor.authorJi, Y
 
dc.contributor.authorSun, S
 
dc.contributor.authorXu, A
 
dc.contributor.authorBhargava, P
 
dc.contributor.authorYang, L
 
dc.contributor.authorLam, KSL
 
dc.contributor.authorGao, B
 
dc.contributor.authorLee, CH
 
dc.contributor.authorKersten, S
 
dc.contributor.authorQi, L
 
dc.date.accessioned2012-08-16T05:54:13Z
 
dc.date.available2012-08-16T05:54:13Z
 
dc.date.issued2012
 
dc.description.abstractNatural killer T (NKT) cells are important therapeutic targets in various disease models and are under clinical trials for cancer patients. However, their function in obesity and type 2 diabetes remains unclear. Our data show that adipose tissues of both mice and humans contain a population of type 1 NKT cells, whose abundance decreases with increased adiposity and insulin resistance. Although loss-of-function of NKT cells had no effect on glucose tolerance in animals with prolonged high fat diet feeding, activation of NKT cells by lipid agonist alpha-galactosylceramide enhances alternative macrophage polarization in adipose tissue and improves glucose homeostasis in animals at different stages of obesity. Furthermore, the effect of NKT cells is largely mediated by the IL-4/STAT6 signaling axis in obese adipose tissue. Thus, our data identify a novel therapeutic target for the treatment of obesity-associated inflammation and type 2 diabetes.
 
dc.description.naturelink_to_OA_fulltext
 
dc.identifier.citationJournal of Biological Chemistry, 2012, v. 287 n. 17, p. 13561-13571 [How to Cite?]
DOI: http://dx.doi.org/10.1074/jbc.M112.350066
 
dc.identifier.doihttp://dx.doi.org/10.1074/jbc.M112.350066
 
dc.identifier.epage13571
 
dc.identifier.hkuros205686
 
dc.identifier.issn0021-9258
2012 Impact Factor: 4.651
2012 SCImago Journal Rankings: 2.723
 
dc.identifier.issue17
 
dc.identifier.openurl
 
dc.identifier.pmcidPMC3340139
 
dc.identifier.pmid22396530
 
dc.identifier.scopuseid_2-s2.0-84859997837
 
dc.identifier.spage13561
 
dc.identifier.urihttp://hdl.handle.net/10722/159707
 
dc.identifier.volume287
 
dc.languageeng
 
dc.publisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/
 
dc.publisher.placeUnited States
 
dc.relation.ispartofJournal of Biological Chemistry
 
dc.rightsJournal of Biological Chemistry. Copyright © American Society for Biochemistry and Molecular Biology, Inc.
 
dc.rightsThis research was originally published in [Journal of Biological Chemistry]. Yi, Y., Sun, S. & Xu, A. Activation of natural killer T cells promotes M2 Macrophage polarization in adipose tissue and improves systemic glucose tolerance via interleukin-4 (IL-4)/STAT6 protein signaling axis in obesity. Journal of Biological Chemistry. 2012. Vol 287:pp 13561-pp 13571. © the American Society for Biochemistry and Molecular Biology
 
dc.subject.meshAdipose Tissue - cytology - metabolism
 
dc.subject.meshGlucose - metabolism
 
dc.subject.meshGlucose Tolerance Test
 
dc.subject.meshKiller Cells, Natural - metabolism
 
dc.subject.meshMacrophages - cytology
 
dc.titleActivation of natural killer T cells promotes M2 Macrophage polarization in adipose tissue and improves systemic glucose tolerance via interleukin-4 (IL-4)/STAT6 protein signaling axis in obesity
 
dc.typeArticle
 
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<item><contributor.author>Ji, Y</contributor.author>
<contributor.author>Sun, S</contributor.author>
<contributor.author>Xu, A</contributor.author>
<contributor.author>Bhargava, P</contributor.author>
<contributor.author>Yang, L</contributor.author>
<contributor.author>Lam, KSL</contributor.author>
<contributor.author>Gao, B</contributor.author>
<contributor.author>Lee, CH</contributor.author>
<contributor.author>Kersten, S</contributor.author>
<contributor.author>Qi, L</contributor.author>
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<description.abstract>Natural killer T (NKT) cells are important therapeutic targets in various disease models and are under clinical trials for cancer patients. However, their function in obesity and type 2 diabetes remains unclear. Our data show that adipose tissues of both mice and humans contain a population of type 1 NKT cells, whose abundance decreases with increased adiposity and insulin resistance. Although loss-of-function of NKT cells had no effect on glucose tolerance in animals with prolonged high fat diet feeding, activation of NKT cells by lipid agonist alpha-galactosylceramide enhances alternative macrophage polarization in adipose tissue and improves glucose homeostasis in animals at different stages of obesity. Furthermore, the effect of NKT cells is largely mediated by the IL-4/STAT6 signaling axis in obese adipose tissue. Thus, our data identify a novel therapeutic target for the treatment of obesity-associated inflammation and type 2 diabetes.</description.abstract>
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Author Affiliations
  1. Harvard School of Public Health
  2. Cornell University
  3. The University of Hong Kong
  4. Wageningen University and Research Centre
  5. National Institute on Alcohol Abuse and Alcoholism