Division of Nutritional Sciences, Cornell University, Ithaca, New York 14853, USA.
J Biol Chem. 2012 Apr 20;287(17):13561-71. doi: 10.1074/jbc.M112.350066. Epub 2012 Mar 6.
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 α-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.
自然杀伤 T（NKT）细胞是各种疾病模型中的重要治疗靶点，目前正在临床试验中用于癌症患者。然而，它们在肥胖和 2 型糖尿病中的功能尚不清楚。我们的数据表明，肥胖症和 2 型糖尿病小鼠和人类的脂肪组织中都含有一群 1 型 NKT 细胞，其丰度随着肥胖和胰岛素抵抗的增加而降低。尽管 NKT 细胞功能丧失对长期高脂肪饮食喂养的动物的葡萄糖耐量没有影响，但脂质激动剂 α-半乳糖神经酰胺激活 NKT 细胞可增强脂肪组织中替代型巨噬细胞的极化，并改善肥胖不同阶段动物的葡萄糖稳态。此外，NKT 细胞的作用主要是通过肥胖脂肪组织中的 IL-4/STAT6 信号通路介导的。因此，我们的数据确定了一种治疗肥胖相关炎症和 2 型糖尿病的新的治疗靶点。
