Abstract: Objective This experiment was conducted to explore effect of liraglutide (Lira) on steatosis in HepG2 cells in vitro. Methods The HepG2 cells were divided into five groups, cell steatosis model were induced by 0.25 mmol/L palmitic acid (PA) incubation, and then intervened by silent information regulator 1(Sirt1) inhibitor, Lira or Sirt1 and Lira combination. Oil red O was stained for lipid droplets, and nicotinamide adenine dinucleotide oxidation/reduced state ratio (NAD⁺/NADH), ALT, AST and triglyceride (TG) contents were determined. Liver kinase B1 (LKB1), free fatty acid (FFA), acetyl-CoA carboxylase (ACC) and adiposetriglyceride lipase (ATGL) mRNA loads were detected by RT-qPCR, and p-adenosine monophosphate-activated protein kinase (AMPK)/sterol regulatory element binding protein 1c(SREBP1c) and p-Sirt1 expression were detected by Western blot. Results Intrahepatocellular lipid droplets were clearly observed in PA-intervened HepG2 cells, which were even more severe in PA/Sirt1-intervened cells, while the lipid droplets obviously reduced in PA/Lira- and PA/Sirt1/Lira-intervened cells, suggesting the model establishment successful and protective effect of Lira; FFA and ACC mRNA loads in PA-intervened cells increased greatly compared to that in control cells (P<0.01), LKB1 and ATGL mRNA loads in PA/Lira-treated cells increased greatly compared to that in PA-treated cells (P<0.001), while FFA and ACC mRNA loads decreased greatly as compared to that in PA-treated cells (P<0.01); LKB1 and ATGL mRNA loads in PA/Sirt1/Lira-treated cells were much higher (P<0.01), while FFA mRNA loads was much lower than in PA/Sirt1-treated cells (P<0.05); p-AMPK and p-Sirt1 protein expression in PA-intervened cells were down-regulated, while SREBP1c expression was up-regulated as compared to that in control cells; p-AMPK expression in PA/Lira-treated cells was up-regulated, while SREBP1c expression was down-regulated compared to that in PA-treated cells; p-AMPK expression in PA/Sirt1/Lira-treated cells was up-regulated compared to that in PA/Sirt1-treated cells. Conclusion Lira could attenuate intracellular fat accumulation in HepG2 cells in vitro, which might be ascribed to direct up-regulation of SIRT1/AMPK signaling pathway or to partially activation of LKB1 leading to increased expression of AMPK protein and inhibition of SREBP1c expression.

Key words: Hep G2 Cells, Liraglutide, Silent information regulator 1, Adenosine monophosphate-activated protein kinase, Steatosis, In vitro