Interleukin-33 induces protective effects in adipose tissue inflammation during obesity in mice.
Interleukin-33 induces protective effects in adipose tissue inflammation during obesity in mice.
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DOI：
10.1161/circresaha.110.218867
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发表时间：
2010-09-03
影响因子：
20.1
通讯作者：
Liew FY
中科院分区：
文献类型：
--
作者：
Miller AM;Asquith DL;Hueber AJ;Anderson LA;Holmes WM;McKenzie AN;Xu D;Sattar N;McInnes IB;Liew FY
涉及脂肪组织的慢性低度炎症可能导致肥胖的代谢后果。细胞因子IL-33及其受体ST2在脂肪组织中表达，但它们在肥胖时脂肪组织炎症中的作用尚不清楚。探讨IL-33在脂肪组织中的功能作用，以及在体内对脂肪组织炎症和肥胖的影响。我们证明，IL-33处理体外培养的脂肪组织可以诱导Th2细胞因子(IL-5、IL-13、IL-10)的产生，并减少成脂和代谢基因的表达。给遗传性肥胖糖尿病(ob/ob)小鼠注射重组IL-33可以减少肥胖，降低空腹血糖，改善葡萄糖和胰岛素耐量。IL-33还诱导脂肪组织中Th2细胞的积聚和脂肪组织巨噬细胞向M2交替激活表型(CD206+)的极化，该表型与防止肥胖相关的代谢事件相关。此外，与饲喂HFD的WT对照组相比，缺乏内源性ST2的饲喂HFD的小鼠体重和脂肪质量增加，胰岛素分泌和血糖调节受损。综上所述，IL-33可能在肥胖时脂肪组织炎症的发生发展中起到保护作用。
Chronic low-grade inflammation involving adipose tissue likely contributes to the metabolic consequences of obesity. The cytokine IL-33 and its receptor ST2 are expressed in adipose tissue but their role in adipose tissue inflammation during obesity is unclear. To examine the functional role of IL-33 in adipose tissues, and investigate the effects on adipose tissue inflammation and obesity in vivo. We demonstrate that treatment of adipose tissue cultures in vitro with IL-33 induced production of Th2 cytokines (IL-5, IL-13, IL-10), and reduced expression of adipogenic and metabolic genes. Administration of recombinant IL-33 to genetically obese diabetic (ob/ob) mice led to reduced adiposity, reduced fasting glucose and improved glucose and insulin tolerance. IL-33 also induced accumulation of Th2 cells in adipose tissue and polarization of adipose tissue macrophages towards an M2 alternatively activated phenotype (CD206+), a lineage associated with protection against obesity-related metabolic events. Furthermore, mice lacking endogenous ST2 fed HFD had increased body weight and fat mass, impaired insulin secretion and glucose regulation compared to WT controls fed HFD. In conclusion, IL-33 may play a protective role in the development of adipose tissue inflammation during obesity.