Abstract:Objective To investigate the effects of N-acetyl-filament-aspartate-Lyophil-proline (AcSDKP) on lipid metabolism in vitro model of nonalcoholic steatohepatitis (NASH) induced by free fatty acid (FFA) in human hepatocyte L02 and its mechanism. Methods L02 cells were divided into control (NC) group, FFA group and AcSDKP treatment groups with different concentrations (FFA+1nM AcSDKP group, FFA+10nM AcSDKP group, FFA+100nM AcSDKP group), lipid deposition of L02 cells in each group was detected by oil red O staining, the content of triglyceride (TG) in L02 cells of each group was detected by the kit, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and malondialdehyde (MDA) in the supernatant of L02 cells of each group were detected by ELISA, the apoptosis rate of L02 cells of each group was detected by Annexin V-FITC/PI double staining method, the mRNA and protein levels of adenylate activated protein kinase (AMPK), fatty acid synthetase (FASN) and sterol regulatory element binding protein-1c (SREBP-1c) in L02 cells of each group were analyzed by real-time fluorescence quantitative PCR and Western blot analysis. Results Compared with FFA group, lipid droplets deposition in L02 cells in FFA+1nM AcSDKP group, FFA+10nM AcSDKP group and FFA+100nM AcSDKP group were significantly decreased, the level of ALT and AST were significantly decreased (P<0.05). MDA content was significantly decreased (P<0.05), apoptosis rate was significantly decreased (P<0.05), AMPK mRNA relative expression level and protein relative expression level were significantly up-regulated (P<0.05), FASN and SERSP-1c mRNA relative expression level and protein relative expression level were significantly down-regulated (P<0.05). Moreover, compared with FFA+1nM AcSDKP group and FFA+10nM AcSDKP group, the lipid deposition in L02 cells in FFA+100nM AcSDKP group was less, and the levels of ALT and AST were also significantly decreased (P<0.05), MDA content was significantly decreased (P<0.05), the apoptosis rate was further decreased (P<0.05), while AMPK protein relative expression was significantly up-regulated (P<0.05), FASN and SERSP-1c mRNA relative expression and protein relative expression were significantly down-regulated (P<0.05). Conclusion AcSDKP can reduce lipid deposition in L02 induced by FFA, promote lipid metabolism and inhibit cell apoptosis, which may be related to the regulation of AMPK/FASN/SERSP-1c expression