Emodin alleviates hepatic steatosis by inhibiting sterol regulatory element binding protein 1 activity by way of the calcium/calmodulin-dependent kinase kinase-AMP-activated protein kinase-mechanistic target of rapamycin-p70 ribosomal S6 kinase signaling pathway.

Abstract

To investigate the effects of emodin on the treatment of non-alcoholic fatty liver and the underlying mechanisms. In vitro, hepatocytes were treated with 1mM free fatty acid together with various concentrations of emodin. In vivo, Sprague-Dawley rats were divided into a control group, high-fat diet (HFD) group, and three HFD groups treated with 40, 80, and 160mg/kg emodin, respectively. After being fed a HFD for 4weeks, rats were orally dosed with emodin once daily for 8weeks. The biochemical parameters and histology features were examined. The expression of lipogenic and lipolytic gene and protein and the phosphorylation of calcium/calmodulin-dependent kinase kinase (CaMKK), AMP-activated protein kinase (AMPK), mechanistic target of rapamycin (mTOR) and p70 ribosomal S6 kinase (p70S6K) were measured in vitro and in vivo. Emodin improved lipid accumulation in vitro and in vivo. Emodin downregulated the levels of sterol regulatory element binding protein 1 (SREBP1) and its target enzymes but increased lipolysis-related proteins and mRNA. Phosphorylation of AMPK was increased, while phosphorylation of mTOR and p70S6K were suppressed by emodin. The nuclear translocation of SREBP1 was inhibited by emodin by AMPK and mTOR. Emodin activated AMPK by CaMKK and reversed the reduction of CaMKK in HFD-fed rats. Emodin effectively ameliorates hepatic steatosis through the CaMKK-AMPK-mTOR-p70S6K-SREBP1 signaling pathway.