In Vitro Experiments Confirmed That Liraglutide Could Improve Non-alcoholic Fatty Liver Disease By Upregulation Of Sirt1/PGC1

Objective: To investigate the therapeutic effect of GLP-1 receptor agonist liraglutide on PA-induced Kupffer cell of NAFLD model.Method:(1)The Kupffer cells of C57BL/6 mice were isolated and extracted and were randomly divided into three groups: ?.blank control group(control group);?.PA treatment group(PA group);?.liraglutide+PA group(treatment group),the concentration of PA was 0.3mmol/l and the liraglutide concentration was 100nmol/l.(2)RT-PCR was used to detect the gene expression levels of NLRP3,ASC,caspase-1,inflammatory cytokines IL-1b,IL-18,TNF-? and signaling pathway Sirt1 and PGC1;Western blot was used to detect the protein level of NLRP3,ASC,caspase-1,Sirt1 and PGC1.The level of the inflammatory cytokine IL-1b,IL-18 and TNF-a of the cell culture supernatant was detected by ELISA.The morphology of mitochondria was observed by electron microscopy.Mitochondrial membrane potential detection kit was used to detect mitochondrial membrane potential of cells in each group.Results: PA increased the expression of NLRP3,ASC and caspase-1 protein and mRNA,while liraglutide had significant inhibitory effect.Compared with the blank group,the level of IL-1b,IL-18 and TNF-a in the supernatant of cells of the PA group rose significantly,however,the level of inflammatory factors decreased after liraglutide treatment.The outcomes of electron microscopy showed that PA treatment could lead to mitochondrial swelling and decreased mitochondrial crest,which was significantly improved after liraglutide treatment.In particularly,the mitochondrial swelling was obvious in the PA group,while reduced in the PA + liraglutide group.After the intervention of liraglutide,the mitochondrial membrane potential was reversed.Further investigation revealed that the reduced Sirt1/PGC1 signaling pathway was up-regulated by liraglutide.Conclusion: Liraglutide can reverse PA-induced Kupffer cell adiposis and the mechanism might be related to the increase of Sirt1/PGC1? level to improve mitochondrial function.