Liraglutide protects non-alcoholic fatty liver disease via inhibiting NLRP3 inflammasome activation in a mouse model induced by high-fat diet

Liraglutide, a glucagon-like peptide-1 (GLP-1) analogue that has recently become the first-line treatment for type 2 diabetes mellitus (T2DM), has also been reported to decrease fatty degeneration of the liver. The purpose of this study is to explore whether liraglutide improves high-fat diet-induced non-alcoholic fatty liver disease (NAFLD) in mice through inhibiting the NLRP3 inflammasome in the liver. After daily intraperitoneal injection of liraglutide (0.6 mg/kg body weight) for four weeks, the liver, liver/body weight, serum levels of ALT, AST, total cholesterol, triglycerides and LDL were significantly decreased in a high-fat diet-induced NAFLD mouse model. The hepatic steatosis among sections of H&E and Oil Red O staining was also markedly reduced after treatment with liraglutide. The expressions of NLRP3 inflammasome components (including NLRP3, ASC, and caspase-1) in the liver of mice after treatment with liraglutide were decreased substantially. In vitro studies found that the mitochondrial dysfunction in Kupffer cells induced by palmitic acid was attenuated, and the protein levels of NLRP3, ASC and caspase-1 were also decrease markedly. These results demonstrate that liraglutide was able to alleviate high-fat diet-induced hepatic steatosis via inhibiting NLRP3 inflammasome activation, suggesting that liraglutide is a potent drug that can reverse the pathological hallmarks of NAFLD.