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
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
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DOI：
10.1074/jbc.m112.350066
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发表时间：
2012-04-20
影响因子：
4.8
通讯作者：
Qi, Ling
中科院分区：
文献类型：
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作者：
Ji, Yewei;Sun, Shengyi;Qi, Ling
自然杀伤T（NKT）细胞是各种疾病模型中的重要治疗靶点，并且正在进行癌症患者的临床试验。然而，它们在肥胖和2型糖尿病中的作用仍不清楚。我们的数据表明，小鼠和人类的脂肪组织都含有1型NKT细胞，其丰度随着肥胖和胰岛素抵抗的增加而减少。虽然NKT细胞功能丧失对长期高脂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巨噬细胞的交替极化，并改善肥胖不同阶段动物的葡萄糖稳态。此外，NKT细胞的作用在很大程度上由肥胖脂肪组织中的IL-4/STAT 6信号传导轴介导。因此，我们的数据确定了治疗肥胖相关炎症和2型糖尿病的新治疗靶点。
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.