期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 287, 期 17, 页码 13561-13571出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M112.350066
关键词
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资金
- National Institutes of Health from NIDDK [R01DK075046]
- NIDDK [R01DK082582, R01DK082582-S1]
- Hong Kong Collaborative Research Fund Grant [HKU4/CRF/10]
- Netherlands Nutrigenomics Centre
- Cornell startup package
- American Diabetes Association [7-08-JF-47, 1-12-CD-04]
- Howard Hughes Medical Institute
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.
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