The Effect Of ANGPTL8 On Nonalcoholic Fatty Liver Disease

Aim: ANGPTL8 is a protein secreted mainly by the liver,which regulates triglyceride metabolism in circulation by inhibiting the activity of lipoprotein lipase.Recent clinical studies have found a positive correlation between serum ANGPTL8 level and the severity of non-alcoholic fatty liver disease,but no causal relationship has been established.In this study,the effects of ANGPTL8 on fatty liver,steatohepatitis and fibrosis in the course of non-alcoholic fatty liver disease were investigated by in vitro and in vivo experiments.Design and methods: The m RNA levels of ANGPTL8 in the liver and plasma ANGPTL8 concentration of NAFLD mice were detected,and the NAFLD model was established respectively in ANGPTL8 overexpressing/knockdown mice to detect the hepatic TG content,liver function,inflammatory cytokine levels,inflammatory cell infiltration and fibrosis in the liver.At the same time,ANGPTL8 was overexpressed or knocked down in the liver cell line AML12 to detect the intracellular TG content and the expression of lipogenic genes.Finally AML12 was co-cultured with the macrophage cell line RAW264.7,and the intracellular TG content was detected after ANGPTL8 recombinant protein was added.Results: The levels of liver ANGPTL8 expression and plasma ANGPTL8 concentration in various NAFLD mouse models were significantly increased(P < 0.05).The hepatic TG content,the levels of liver enzymes and inflammatory cytokines were significantly increased in ANGPTL8 overexpressing mice and decreased in ANGPTL8 knockdown mice.The intracellular TG content and lipogenic gene expression was unchanged between the AML12 cells overexpressing or knocking down ANGPTL8 and the control group,but was significantly increased in the AML12 cells co-cultured with RAW264.7 cells after ANGPTL8 was added.Conclusion: ANGPTL8 expression increased significantly in nonalcoholic fatty liver disease.ANGPTL8 can increase the infiltration of inflammatory cells in the liver,promote the generation of inflammatory cytokine and liver cell damage,and can promote hepatic steatosis by macrophages,thus plays an important role in nonalcoholic fatty liver disease.