Rev-erbα exacerbates hepatic steatosis in alcoholic liver diseases through regulating autophagy

Cell & Bioscience

Jun Li¹  Cheng Huang¹  Yiwen Zhou¹  Lei Xu¹  Lei Zhang¹  Meifei Wu¹  Qingxue Liu¹  Tao Xu¹  Junfa Yang¹ 

[1] School of Pharmacy, Anhui Institute of Innovative Drugs, Anhui Medical University, 230032, Hefei, Anhui, China;Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, 230032, Hefei, People’s Republic of China;The Key Laboratory of Anti-Inflammatory and Immune Medicines, Ministry of Education, 230032, Hefei, China;

关键词: Rev-erbα;    AFL;    Autophagy;    Bmal1;    Lysosome;   

DOI  :  10.1186/s13578-021-00622-4

来源: Springer

【 摘 要 】

Background and aimsAlcoholic fatty liver (AFL) is a liver disease caused by long-term excessive drinking and is characterized by hepatic steatosis. Understanding the regulatory mechanism of steatosis is essential for the treatment of AFL. Rev-erbα is a member of the Rev-erbs family of nuclear receptors, playing an important role in regulating lipid metabolism. However, its functional role in AFL and its underlying mechanism remains unclear.ResultsRev-erbα was upregulated in the liver of EtOH-fed mice and EtOH-treated L-02 cells. Further, Rev-erbα activation exacerbates steatosis in L-02 cells. Inhibition/downexpression of Rev-erbα improved steatosis. Mechanistically, autophagy activity was inhibited in vivo and vitro. Interestingly, inhibition/downexpression of Rev-erbα enhanced autophagy. Furthermore, silencing of Rev-erbα up-regulated the nuclear expression of Bmal1. Autophagy activity was inhibited and steatosis was deteriorated after EtOH-treated L-02 cells were cotransfected with Rev-erbα shRNA and Bmal1 siRNA.ConclusionsRev-erbα induces liver steatosis, which promotes the progression of AFL. Our study reveals a novel steatosis regulatory mechanism in AFL and suggest that Rev-erbα might be a potential therapeutic target for AFL.

【 授权许可】

CC BY