Natural Killer T Cells Are Involved in Adipose Tissues Inflammation and Glucose Intolerance in Diet-Induced Obese Mice

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Objective: Macrophage as well as lymphocyte infiltration in adipose tissue may contribute to the pathogenesis of obesity-mediated metabolic disorders. Natural killer T (NKT) cells, which integrate proinflammatory cytokines, have been demonstrated in the atherosclerotic lesions and also in visceral adipose tissue. We thus determined whether NKT cells are involved in glucose intolerance and adipose tissue inflammation in diet-induced obese mice. Methods and Results: To determine whether NKT cells are involved in the development of glucose intolerance, male β2 microglobulin knockout mice lacking NKT cells (KO) and C57BL/6J (WT) mice were fed with a high fat diet (HFD) for 13 weeks. Body weight and visceral obesity were comparable between WT and KO mice. However, macrophage infiltration was reduced in adipose tissue and glucose intolerance was significantly ameliorated in KO mice. To further confirm that NKT cells are involved in these abnormalities, α-galactosylceramide (αGC, 0.1μg/g body weight), which specifically activates NKT cells, were administered after 13 weeks of HFD feeding. αGC significantly exacerbated glucose intolerance and also macrophage infiltration as well as cytokine gene expression in adipose tissue. Conclusions: NKT cells play a crucial role in the development of adipose tissue inflammation and glucose intolerance in diet-induced obesity.
2010-02-01

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