Angiotensin‐(1‐7) improves non‐alcoholic steatohepatitis through an adiponectin‐independent mechanism

AIM: Recent evidence suggests that angiotensin-(1-7) [Ang-(1-7)] could improve non-alcoholic steatohepatitis (NASH) through an adiponectin-dependent mechanism. This study aimed to investigate whether and how Ang-(1-7) influences NASH without adiponectin. METHODS: Adiponectin knockout mice were fed with a high fat diet (HFD) or normal chow for 6 months, and were subsequently infused with Ang-(1-7) or saline for 2 weeks. RESULTS: We found that HFD-fed mice showed 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. In addition, Ang-(1-7) treatment could attenuate hepatocellular inflammation, steatosis, and ballooning with activation of the hepatic AMP-activated protein kinase signaling pathway in HFD-fed knockout mice. CONCLUSIONS: These results showed the protective role of Ang-(1-7) in the development of NASH through an adiponectin-independent mechanism, which may be partially attributed to the activation of hepatic AMP-activated protein kinase pathway.