Angiotensin-(1-7) Improves Non-alcoholic Steatohepatitis Via An Adiponectin-independent Mechanism

Objective : Recent evidences suggest that angiotensin-(1-7)[Ang-(1-7)] could improve non-alcoholic steatohepatitis(NASH) via adiponectin-dependent mechanism. This study was aimed to investigate whether and how Ang-(1-7) influences NASH without adiponectin.Methods : Adiponectin knockout(KO) mice were fed with high fat diet(HFD) or normal chow for six months, subsequently infused with Ang-(1-7) or saline for two weeks. Then, Body weight, liver weight,triglyceride(TC), total cholesterol(TG), low density lipoprotein cholesterol(LDL-C), Aspartate aminotransferase(AST), Alanine aminotransferase(ALT), Ang-(1-7), hepatic histology, expression of AMP-activated protein kinase α2(AMPKα2), Glucose transporter type-2(GLUT2), Sterol regulatory element-binding protein-1(SREBP1) mRNA and phosphorylated AMP-activated protein kinase(p-AMPK),stearoyl-CoA desaturase-1(SCD1), phosphoenolpyruvate carboxykinase-2(PCK2) protein levels in liver tissue were measured at sacrifice.Results : We found that HFD fed mice exhibited obesity,hyperlipidemia, NASH, and significantly increased levels of serum Ang-(1-7). Chronic infusion of Ang-(1-7) could reduce body weight,absolute and relative liver weight, and serum levels of total cholesterol,triglyceride and low-density lipoprotein cholesterol in HFD fed mice.Besides, Ang-(1-7) treatment could attenuate hepatocellular inflammation,steatosis and ballooning with activation of hepatic AMPK signaling pathway in HFD fed KO mice.Conclusions : These results demonstrated the protective role of Ang-(1-7) in the development of NASH through adiponectin-independent mechanism, which may partially attribute to the activation of hepatic AMPK pathway.