Effects and mechanisms of resveratrol on the amelioration of oxidative stress and hepatic steatosis in KKAy mice

Background: The exact mechanism of the protective role of Resveratrol (Res) in lipid metabolism and oxidative stress is not well elucidated. The present study aimed to investigate the potential benefits and possible mechanisms of Res on the amelioration of oxidative stress and hepatic steatosis in a KKAy mouse model. Methods: A total of 30 KKAy male mice were randomly divided into three groups: a normal chow group, a low resveratrol group and a high resveratrol group. After a 12-wk study period, serum levels of TG, TC, LDL-C and HDL-C, the liver content of TG and TC, ROS, GSH, GPx, SOD and MDA levels were measured. Ectopic lipid deposition was observed in sectioned frozen liver tissues. The mRNA levels of ATGL and HSL in the liver tissues were determined via real-time PCR. Furthermore, the protein expression of p47phox, gp91phox, ATGL, HSL, Sirt1, AMPK and FOXO1 were analyzed using western blotting. Results: Following Res supplementation, serum levels of TG and MDA were decreased, while the HDL-C and SOD levels were increased in KKAy mice. Furthermore, Res treatment increased GSH and GPx in liver tissues, while it decreased ROS. In addition, Res significantly reduced hepatic steatosis. After Res treatment, concentrations of p47phox (membrane) and gp91phox proteins were reduced, while p-HSL, HSL and ATGL protein expression levels were increased. Mechanistically, the levels of Sirt1, p-AMPK and p-FOXO1 expression in the liver tissues were up-regulated following supplementation with Res, and FOXO1 protein was released from the nucleus into the cytoplasm. Conclusions: Res is able to attenuate hepatic steatosis and lipid metabolic disorder and enhance the antioxidant ability in KKAy mice, possibly by up-regulating Sirt1 expression and the phosphorylation of AMPK.