切梅林
脂肪组织
先天免疫系统
产热
内分泌学
内科学
免疫
脂肪因子
脂肪细胞
生物
趋化因子
免疫系统
免疫学
医学
肥胖
胰岛素抵抗
作者
Yu‐Li Lin,Liuling Xiao,Qian Cai,Cuisong Zhu,Shufen Li,Bingji Li,Ting Liu,Qiongyue Zhang,Yi Wang,Yiming Li,Xing He,Dongning Pan,Qi‐Qun Tang,Xiaohui Wu,Weiqing Pan,Jiqiu Wang,Xi Li,Rui He
出处
期刊:Science immunology
[American Association for the Advancement of Science (AAAS)]
日期:2021-07-29
卷期号:6 (61)
被引量:18
标识
DOI:10.1126/sciimmunol.abg9698
摘要
IL-33-associated type 2 innate immunity has been shown to support beige fat formation and thermogenesis in subcutaneous inguinal white adipose tissue (iWAT), but little is known about how it is regulated in iWAT. Chemerin, as a newly identified adipokine, is clinically associated with obesity and metabolic disorders. We here show that cold exposure specifically reduces chemerin and its receptor chemerin chemokine-like receptor 1 (CMKLR1) expression in iWAT. Lack of chemerin or adipocytic CMKLR1 enhances cold-induced thermogenic beige fat via potentiating type 2 innate immune responses. Mechanistically, we identify adipocytes, particularly beige adipocytes, as the main source for cold-induced IL-33, which is restricted by the chemerin-CMKLR1 axis via dampening cAMP-PKA signaling, thereby interrupting a feed-forward circuit between beige adipocytes and type 2 innate immunity that is required for cold-induced beige fat and thermogenesis. Moreover, specific deletion of adipocytic IL-33 inhibits cold-induced beige fat and type 2 innate immune responses. Last, genetic blockade of adipocytic CMKLR1 protects against diet-induced obesity and enhances the metabolic benefits of cold stimulation in preestablished obese mice. Thus, our study identifies the chemerin-CMKLR1 axis as a physiological negative regulator of thermogenic beige fat via interrupting adipose-immune communication and suggests targeting adipose CMKLR1 as a potential therapeutic strategy for obesity-related metabolic disorders.
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