2. Academic Validation
  3. CD9 Counteracts Liver Steatosis and Mediates GCGR Agonist Hepatic Effects

CD9 Counteracts Liver Steatosis and Mediates GCGR Agonist Hepatic Effects

  • Adv Sci (Weinh). 2024 Jun 5:e2400819. doi: 10.1002/advs.202400819.
Yi Zheng 1,  Yuren Wang 1,  Xin Xiong 1,  Linlin Zhang 1,  Jiaran Zhu 1,  Bangliang Huang 1,  Xiufei Liu 1,  Jinbo Liu 2,  Zhiming Zhu 3,  Gangyi Yang 4,  Hua Qu 1,  Hongting Zheng 1
Affiliations

Affiliations

  • 1 Department of Endocrinology, Translational Research of Diabetes Key Laboratory of Chongqing Education Commission of China, the Second Affiliated Hospital of Army Medical University, Chongqing, 400037, China.
  • 2 Department of Endocrinology, Qilu Hospital of Shandong University, Jinan, 250012, China.
  • 3 Department of Hypertension and Endocrinology, the Third Affiliated Hospital of Army Medical University, Chongqing, 400042, China.
  • 4 Department of Endocrinology, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.
PMID: 38837628 DOI: 10.1002/advs.202400819
Abstract

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.

Keywords

glucagon receptor signaling; hepatic steatosis; lipid metabolism; tetraspanin CD9.

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