CD9 Counteracts Liver Steatosis and Mediates GCGR Agonist Hepatic Effects

作者全名："Zheng, Yi; Wang, Yuren; Xiong, Xin; Zhang, Linlin; Zhu, Jiaran; Huang, Bangliang; Liu, Xiufei; Liu, Jinbo; Zhu, Zhiming; Yang, Gangyi; Qu, Hua; Zheng, Hongting"

作者地址："[Zheng, Yi; Wang, Yuren; Xiong, Xin; Zhang, Linlin; Zhu, Jiaran; Huang, Bangliang; Liu, Xiufei; Qu, Hua; Zheng, Hongting] Army Med Univ, Affiliated Hosp 2, Chongqing Educ Commiss China, Dept Endocrinol,Translat Res Diabet Key Lab, Chongqing 400037, Peoples R China; [Liu, Jinbo] Shandong Univ, Qilu Hosp, Dept Endocrinol, Jinan 250012, Peoples R China; [Zhu, Zhiming] Army Med Univ, Affiliated Hosp 3, Dept Hypertens & Endocrinol, Chongqing 400042, Peoples R China; [Yang, Gangyi] Chongqing Med Univ, Affiliated Hosp 2, Dept Endocrinol, Chongqing 400010, Peoples R China"

通信作者："Zheng, Y; Qu, H; Zheng, HT (通讯作者)，Army Med Univ, Affiliated Hosp 2, Chongqing Educ Commiss China, Dept Endocrinol,Translat Res Diabet Key Lab, Chongqing 400037, Peoples R China."

来源：ADVANCED SCIENCE

ESI学科分类：PHYSICS

WOS号：WOS:001238761800001

JCR分区：Q1

影响因子：15.1

年份：2024

卷号：11

期号：29

开始页：　

结束页：　

文献类型：Article

关键词：glucagon receptor signaling; hepatic steatosis; lipid metabolism; tetraspanin CD9

摘要："Glucagon receptor (GCGR) agonism offers potentially greater effects on the mitigation of hepatic steatosis. However, its underlying mechanism is not fully understood. Here, it screened tetraspanin CD9 might medicate hepatic effects of GCGR agonist. CD9 is decreased in the fatty livers of patients and upregulated upon GCGR activation. Deficiency of CD9 in the liver exacerbated diet-induced hepatic steatosis via complement factor D (CFD) regulated fatty acid metabolism. Specifically, CD9 modulated hepatic fatty acid synthesis and oxidation genes through regulating CFD expression via the ubiquitination-proteasomal degradation of FLI1. In addition, CD9 influenced body weight by modulating lipogenesis and thermogenesis of adipose tissue through CFD. Moreover, CD9 reinforcement in the liver alleviated hepatic steatosis, and blockage of CD9 abolished the remission of hepatic steatosis induced by cotadutide treatment. Thus, CD9 medicates the hepatic beneficial effects of GCGR signaling, and may server as a promising therapeutic target for hepatic steatosis. Current study revealed that hepatic deficiency of CD9 exacerbated diet-induced liver steatosis via complement factor D regulated fatty acid metabolism. Hepatic CD9 reinforcement alleviated liver steatosis, and blockage of CD9 abolished the remission of hepatic steatosis induced by cotadutide treatment. CD9 medicates the hepatic beneficial effects of GCGR signaling, and may server as a promising therapeutic target for hepatic steatosis. image"

基金机构："National Natural Science Foundation of China [82122013, 81925007, 82230025, 82100910, 82070881, 82000769, 82070836]; Chongqing Distinguished Young Scholars [CSTB2022NSCQ-JQX0002]; Talent Projec of Army Medical University [2022YQB007, 2019XQYYYJ003-2, 2019R012, 2019R047]"

基金资助正文："This work was supported by the National Natural Science Foundation of China (Nos. 82122013, 81925007, 82230025, 82100910, 82070881, 82000769, and 82070836), the Chongqing Distinguished Young Scholars (CSTB2022NSCQ-JQX0002), and the ""Talent Project"" of Army Medical University (2022YQB007, 2019XQYYYJ003-2, 2019R012 and 2019R047)."