[Liraglutide alleviates lipotoxic liver cell damage and promotes autophagy to improve non-alcoholic fatty liver].

Objective: To study the effect of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on free fatty acid (FFA)-induced hepatocyte steatosis, and to explore its autophagic role in this process. Methods: Human hepatocytes were cultured in vitro to induce NAFLD cell model. Liraglutide (LRG) concentration gradient was added to observe the effect on cell survival rate and fatty degeneration of liver cells. The relationship between liraglutide and autophagy was investigated with chloroquine inhibition and rapamycin (RAPA) activation in hepatocyte steatosis. Experimental group: control group: a certain concentration of BSA was added to cells cultured in DMEM complete medium; FFA model group: fatty degeneration of hepatocytes was induced by 1mmol/L FFA (OA : PA=2 : 1); LRG group: FFA (1 mmol/L) and LRG (100 nmol/L) were added to the cells at the same time; autophagy inhibition group: FFA (1 mmol/L), LRG (100 nmol/L), and chloroquine (20 μmol/L) were added to the cells at the same time; autophagy activated group: FFA (1 mmol/L) and RAPA (1 μmol/L) were added to the cells at the same time. Oil red O staining and fully automated biochemistry analyzer were used to observe the intracellular lipidosis condition. Western blotting was used to detect the levels of autophagy-related proteins (Beclin1, P62, and LC3B). One-way analysis of variance was used to compare the means between multiple groups. Results: Within a certain concentration range, with the increase of LRG concentration, the hepatocytes survival rate was increased and the degree of intracellular lipidosis had continued to decrease. The best effect was achieved when LRG concentration reached 100nmol/L, and the difference was statistically significant when compared with the FFA group ( P < 0.01). During the exploration of the relationship between the degree of hepatic steatosis and autophagy, LRG group intracellular triglyceride content was significantly lower than FFA group ( P < 0.01), and the levels of Beclin1, LC3B-II/LC3B-I were higher than FFA group. Additionally, FFA group had reduced P62 level, and enhanced autophagy. Compared with the LRG group, autophagy inhibition group intracellular triglyceride content was increased ( P < 0.01), while the levels of Beclin1, LC3B-II/LC3B-I was decreased, and P62 level was increased. Autophagy activated group RAPA had significantly reduced FFA-induced intrahepatic triglyceride deposition, and the changes in autophagy-related protein levels were consistent with the effect of LRG. Conclusion: GLP-1RAs can alleviates FFA-induced lipotoxic liver cell damage, and promote autophagy to improve fatty degeneration of hepatocytes in NAFLD.