Metformin Alleviates Steatohepatitis in Diet-Induced Obese Mice in a SIRT1-Dependent Way

Frontiers in Pharmacology

Juan Liu¹  Li-dan Cheng²  Xiao-bin Zheng⁴  Hua Liang⁵  Fen Xu⁵  Wan-rong Guo⁵  Zi-yu Liu⁵ 

[1] Department of Endocrinology and Metabolism, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China;Department of Endocrinology and Metabolism, the Second Affiliated Hospital of Nanchang University, Nanchang, China;Department of Endocrinology and Metabolism, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China;Department of Gastroenterology, Shantou Central Hospital, Shantou, Guangdong, China;Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, China;

关键词: meformin;    SIRT1;    NAFLD;    M1 polarization;    cholesterol catabolism;   

DOI  :  10.3389/fphar.2021.704112

来源: DOAJ

【 摘 要 】

Metformin is the first-line anti-diabetic drug for type 2 diabetes. It has been found to significantly reduce liver aminotransferase in nonalcoholic fatty liver disease (NAFLD). However, whether metformin improves NAFLD progression remains controversial. Sirtuin 1 (SIRT1), an NAD+-dependent deacetylase, plays a vital role in hepatic steatosis and inflammation. Here, we investigated the effect of metformin on steatohepatitis and the role of SIRT1 in diet-induced obese (DIO) mice. The results showed that metformin significantly reduced body weight and fat mass of DIO mice. In addition, metformin also alleviated adiposity and hepatic steatosis, and greatly upregulated uncoupling protein 1 (UCP1) expression in adipose tissues of DIO mice. Unexpectedly, the effects of metformin on reducing body weight and alleviating hepatic steatosis were not impaired in Sirt1 heterozygous knockout (Sirt1+/−) mice. However, SIRT1-deficiency remarkably impaired the effects of metformin on lowering serum transaminases levels, downregulating the mRNA expression of proinflammatory factors, and increasing the protein level of hepatic Cholesterol 25-Hydroxylase (CH25H), a cholesterol hydroxylase in cholesterol catabolism. In summary, we demonstrated that metformin alleviates steatohepatitis in a SIRT1-dependent manner, and modulation of M1 polarization and cholesterol metabolism may be the underlying mechanism.

【 授权许可】

Unknown