CMKLR1 senses chemerin/resolvin E1 to control adipose thermogenesis and modulate metabolic homeostasis  

作　　者：Zewei Zhao Siqi Liu Bingxiu Qian Lin Zhou Jianglin Shi Junxi Liu Lin Xu Zhonghan Yang 

机构地区：[1]Department of Biochemistry,Molecular Cancer Research Center,School of Medicine,Sun Yat-sen University,Shenzhen,Guangdong 518107,China [2]Department of Biochemistry,Zhongshan School of Medicine,Sun Yat-sen University,Guangzhou,Guangdong 510080,China [3]School of Public Health,Sun Yat-sen University,Guangzhou,Guangdong 510080,China

出　　处：《Fundamental Research》2024年第3期575-588,共14页自然科学基础研究（英文版）

基　　金：funded by the National Natural Science Foundation of China(81570764);Guangzhou Science and Technology Project(201807010069);Shenzhen Science and Technology Project(JCYJ20190807154205627);Guangdong Natural Science Fund(2020A1515010365);Guangdong Provincial Key Laboratory of Precision Medicine and Clinical Translation Research of Hakka Population(2018B030322003KF01)received by Zhonghan Yang。

摘　　要：Induction of beige fat for thermogenesis is a potential therapy to improve homeostasis against obesity.β3-adrenoceptor(β3-AR),a type of G protein-coupled receptor(GPCR),is believed to mediate the thermogenesis of brown fat in mice.However,β3-AR has low expression in human adipose tissue,precluding its activation as a standalone clinical modality.This study aimed at identifying a potential GPCR target to induce beige fat.We found that chemerin chemokine-like receptor 1(CMKLR1),one of the novel GPCRs,mediated the development of beige fat via its two ligands,chemerin and resolvin E1(RvE1).The RvE1 levels were decreased in the obese mice,and RvE1 treatment led to a substantial improvement in obese features and augmented beige fat markers.Inversely,despite sharing the same receptor as RvE1,the chemerin levels were increased in obesogenic conditions,and chemerin treatment led to an augmented obese phenotype and a decline of beige fat markers.Moreover,RvE1 and chemerin induced or restrained the development of beige fat,respectively,via the mechanistic target of rapamycin complex 1(mTORC1)signaling pathway.We further showed that RvE1 and chemerin regulated mTORC1 signaling differentially by forming hydrogen bonds with different binding sites of CMKLR1.In conclusion,our study showed that RvE1 and chemerin affected metabolic homeostasis differentially,suggesting that selectively modulating CMKLR1 may be a potential therapeutic target for restoring metabolic homeostasis.

关 键 词：Obesity Insulin resistance THERMOGENESIS CMKLR1 Resolvin E1 CHEMERIN 

分 类 号：R589.2[医药卫生—内分泌]