Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305-5324, USA.
J Immunol. 2010 Dec 1;185(11):6947-59. doi: 10.4049/jimmunol.1001269. Epub 2010 Oct 29.
Inflammatory mediators have the potential to impact a surprising range of diseases, including obesity and its associated metabolic syndrome. In this paper, we show that the proinflammatory cytokine IL-17 inhibits adipogenesis, moderates adipose tissue (AT) accumulation, and regulates glucose metabolism in mice. IL-17 deficiency enhances diet-induced obesity in mice and accelerates AT accumulation even in mice fed a low-fat diet. In addition to potential systemic effects, IL-17 is expressed locally in AT by leukocytes, predominantly by γδ T cells. IL-17 suppresses adipocyte differentiation from mouse-derived 3T3-L1 preadipocytes in vitro, and inhibits expression of genes encoding proadipogenic transcription factors, adipokines, and molecules involved in lipid and glucose metabolism. IL-17 also acts on differentiated adipocytes, impairing glucose uptake, and young IL-17-deficient mice show enhanced glucose tolerance and insulin sensitivity. Our findings implicate IL-17 as a negative regulator of adipogenesis and glucose metabolism in mice, and show that it delays the development of obesity.
炎症介质有可能影响到一系列令人惊讶的疾病，包括肥胖症及其相关的代谢综合征。在本文中，我们表明促炎细胞因子 IL-17 可抑制脂肪生成、适度脂肪组织 (AT) 积累，并调节小鼠的葡萄糖代谢。IL-17 缺乏会增强小鼠的饮食诱导肥胖，并加速 AT 积累，即使在低脂饮食喂养的小鼠中也是如此。除了可能的全身作用外，IL-17 还由白细胞在 AT 中局部表达，主要由 γδ T 细胞表达。IL-17 在体外抑制来自小鼠来源的 3T3-L1 前体脂肪细胞的脂肪细胞分化，并抑制编码前脂肪生成转录因子、脂肪因子和参与脂质和葡萄糖代谢的分子的表达。IL-17 还作用于分化的脂肪细胞，损害葡萄糖摄取，年轻的 IL-17 缺陷型小鼠表现出增强的葡萄糖耐量和胰岛素敏感性。我们的研究结果表明，IL-17 是小鼠脂肪生成和葡萄糖代谢的负调节剂，并表明它可延迟肥胖的发展。
