Sodium Orthovanadate Mitigates Nonalcoholic Fatty Liver Disease by Enhancing Autophagy.

Abstract

Sodium orthovanadate (SOV) has been investigated in recent research for its therapeutic efficacy in treating metabolic disorders. Considering the rising prevalence of non-alcoholic fatty liver disease (NAFLD), the effects of SOV on NAFLD remain to be further investigated. The aim of this study was to investigate the role and mechanism of SOV in NAFLD. Two mouse models were established by induction with high fat diet (HFD) and Western diet supplemented with the sugar in drinking water (WDS), respectively. We searched for the downstream molecules of SOV by RNA sequencing, followed by rescue experiments with an autophagy inhibitor (3-MA) in HepG2 cells as well as in animal models. The results showed that in HFD and WDS-induced NAFLD models, SOV significantly reduced body weight, inhibited lipid deposition, lowered serum triglyceride and cholesterol levels. Then RNA sequencing and RT-PCR found that the effect of SOV might be related to the activation of autophagy coregulated by hypoxia-inducible factor 1 and autophagy-related gene 5. The protective effects of SOV-activated autophagy were blocked by 3-MA, leading to the restoration of lipid deposition in vitro and in vivo. We conclude that SOV could activate liver cell autophagy, thereby improving lipid deposition and metabolism during the course of NAFLD. Our findings revealed the potential of SOV for controlling NAFLD.