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 signalling axis in obesity

Y. Ji, S. Sun, Aimin Xu, P. Bhargava, Liu Yang, K.S.L. Lam, Bin Gao, Chih-Hao Lee, A.H. Kersten, L. Qi

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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 a-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.
Original languageEnglish
Pages (from-to)13561-13571
Number of pages11
JournalJournal of Biological Chemistry
Volume287
Issue number17
DOIs
Publication statusPublished - 2012

Keywords

  • invariant nkt cells
  • insulin-resistance
  • alternative activation
  • microbial infection
  • mice
  • inflammation
  • receptor
  • pathway
  • disease
  • fat

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    Activation of natural killer T cells promotes M2 macrophage polarization in adipose tissue and improves systemic glucose tolerance via the IL-4/STAT6 signaling axis in obesity

    Ji, Y. (Creator), Sun, S. (Creator), Xu, A. (Creator), Yang, L. (Creator), Bhargava, P. (Creator), Lam, K. S. (Creator), Gao, B. (Creator), Lee, C. (Creator), Kersten, S. (Creator) & Qi, L. (Creator), Wageningen University, 13 Apr 2012

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