Administration of methyl palmitate prevents non-alcoholic steatohepatitis (NASH) by induction of PPAR-α

Background and aims: The lack of valid therapeutic approach that can ameliorate the manifestations of NASH is a barrier to therapeutic development. Therefore, we investigate the novel role of Methyl Palmitate (MP) in preventing NASH and the possible mechanism involved. Methods: 50 Male C57BL/6 J mice were randomly divided into 5 groups (n = 10). The control group was fed control diet; model group was fed MCD diet; MP 1 group was fed MCD diet supplemented with MP (75 mg/kg/day); MP 2 group was fed MCD plus MP diet (150 mg/kg/day); and MP 3 group was fed MCD plus MP diet (300 mg/kg/day). Histological staining's, and commercially available kits for serum ALT and AST and hepatic contents of TG, TC, MDA, SOD, and GSH were used to assess NASH. Furthermore, relative liver protein and gene expression levels were determined by Western Blot and qPCR, respectively. Results: Mice fed MCD diet developed NASH, which was markedly improved by MP in a dose-dependent manner. MP treatment improved hepatic content of TG, TC, MDA, SOD and GSH and serum levels of ALT and AST. In vivo studies showed that MP treatment activated PPAR alpha expression, that in turns, promoted beta-oxidation protein and gene expressions, suppressed TNF alpha, MCP1, TGF beta 1 and Colla1 protein and gene expression levels, contributing to the prevention of NASH. Conclusions: Our results indicated that MP could successfully prevent NASH. This effect of MP was mediated through induction of PPAR alpha pathway. This study provides a novel therapeutic target that plays pivotal role in the prevention of NASH.