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

被引：174

作者：

Ji, Yewei ^{[1
]}

Sun, Shengyi ^{[2
]}

Xu, Aimin ^{[3
,4
]}

Bhargava, Prerna ^{[5
,6
]}

Yang, Liu ^{[2
]}

Lam, Karen S. L. ^{[3
,4
]}

Gao, Bin ^{[7
]}

Lee, Chih-Hao ^{[5
,6
]}

Kersten, Sander ^{[1
,8
]}

Qi, Ling ^{[1
,2
]}

机构：

[1] Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA

[2] Cornell Univ, Grad Program Biochem Mol & Cell Biol, Ithaca, NY 14853 USA

[3] Univ Hong Kong, Dept Med, Hong Kong, Hong Kong, Peoples R China

[4] Univ Hong Kong, Ctr Heart Brain Hormone & Hlth Aging, Hong Kong, Hong Kong, Peoples R China

[5] Harvard Univ, Sch Publ Hlth, Dept Genet, Boston, MA 02115 USA

[6] Harvard Univ, Sch Publ Hlth, Dept Complex Dis & Nutr, Boston, MA 02115 USA

[7] NIAAA, Lab Liver Dis, Rockville, MD 20852 USA

[8] Wageningen Univ, Div Human Nutr, Nutr Metab & Genom Grp, NL-6700 EV Wageningen, Netherlands

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2012年 / 287卷 / 17期

基金：

美国国家卫生研究院;

关键词：

INVARIANT NKT CELLS; ALTERNATIVE ACTIVATION; INSULIN-RESISTANCE; LIPID ANTIGEN; INFLAMMATION; RECEPTOR; MICE; FAT; RECOGNITION; MODULATION;

D O I：

10.1074/jbc.M112.350066

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：13561 / 13571

页数：11

共 57 条

[1] Lysosomal recycling terminates CD1d-mediated presentation of short and polyunsaturated variants of the NKT cell lipid antigen αGalCer [J].