Sweroside alleviates hepatic steatosis in part by activating AMPK/mTOR-mediated autophagy in mice.

Abstract

In this study, we investigated the effect of sweroside (SOS)on hepatic steatosis in mice and elucidated its molecular mechanisms. We conducted in vivo experiments using a C57BL/6 mice model of nonalcohol fatty liver disease (NAFLD)to explore the effect of SOS on hepatic steatosis in NAFLD mice. In in vitro experiments, primary mouse hepatocyteswere treated with palmitic acidand SOS, and the protective effects of SOS on inflammation, lipogenesis, and fat deposition were analyzed. Autophagy-related protein levels and their related signaling pathways were evaluated in both in vivo and in vitro experiments. The results demonstrated that SOS decreased the high-fat-induced intrahepatic lipid content both in vivo and in vitro. The autophagy level in the liver was decreased in NAFLD mice but was reactivated following SOS intervention. SOS intervention was found to partially activate autophagy via the adenosine monophosphate-activated protein kinase (AMPK)/mammaliantarget of rapamycin (mTOR)signaling pathway. Consequently, when the AMPK/mTORpathway was suppressed or autophagy was inhibited, the beneficial effects of SOS intervention on hepatic steatosis were diminished. These results indicate that SOS intervention attenuates hepatic steatosis by promoting autophagy in the liver of NAFLD mice, in part by activating the AMPK/mTOR signaling pathway.