Ginsenoside Rg2 ameliorates high-fat diet-induced metabolic disease through SIRT1.

Ginsenoside Rg2 has been previously reported to reduce glucose production and adipogenesis in adipose tissue. However, the effects of ginsenosides Rg2 on hepatic lipid metabolism remains vacant. In this study, we found that ginsenosides Rg2 treatment significantly attenuated oleic acid and palmitic acid (OA&PA) induced intracellular lipid deposition and oxidative stress in mouse primary hepatocytes. C57BL/6J mice fed a high-fat diet (HFD) and treated with ginsenosides Rg2 displayed decreased body weight, reversed hepatic steatosis and improved glucose tolerance and insulin sensitivity. Ginsenosides Rg2 administration significantly ameliorated HFD-induced hepatic oxidative stress and apoptosis. Moreover, Ginsenosides Rg2 had a good affinity with Sirtuin1 (SIRT1) and regulated its expression in vivo and in vitro. Deficiency of SIRT1 eliminated the therapeutic effect of ginsenoside Rg2 on lipid accumulation and overproduction of reactive oxygen species (ROS) in OA&PA-induced mice primary hepatocytes. Ginsenosides Rg2 treatment failed to alter the lipid and glucose disorder in hepatic SIRT1 deficient mice feeding on HFD. SIRT1 deficiency dissolves the therapeutic effect of ginsenoside Rg2 on oxidative stress and hepatocyte apoptosis induced by HFD. In summary, ginsenoside Rg2 plays a therapeutic role in HFD-induced hepatosteatosis of mice by decreasing lipogenesis process and improving antioxidant capacity in a SIRT1 dependent manner.