Study Of The Functions And Mechanisms Of DJ-1 In Nonalcoholic Fatty Liver Disease

Aims:Non-alcoholic fatty liver disease（NAFLD）can develop into non-alcoholic steatohepatitis（NASH）,liver cirrhosis and even liver cancer,which has become a common chronic disease that endangers human health.However,there is no effective drug for the treatment of NAFLD at present.The research on pathogenesis,new drugs and new targets for NAFLD are particularly urgent.Abnormalities in various aspects of the synthesis and decomposition of liver lipids can cause NAFLD,and oxidative stress damage plays an important role.Recent studies have shown that DJ-1,as a traditional anti-oxidative stress injury molecule,plays an important role in various liver diseases including liver fibrosis,liver injury and liver cancer by regulating oxidative stress and inflammatory response.The purpose of this study was to investigate the function and mechanism of DJ-1 in NAFLD.Methods:The wild-type（WT）mice and DJ-1 knockout(DJ-1^-/-)mice were fed with60%high-fat diet（HFD）for 24 weeks to establish an animal model of fatty liver.We monitored Body weight change,insulin sensitivity and liver lipid accumulation in mice by biochemical test,HE staining,oil red O staining,weighing body weight,epididymal fat weight and liver weight,glucose and insulin tolerance test.Western Blot,PCR and other methods were used to detect the changes of key enzyme genes in various metabolic pathways of the liver.Results:Ablation of DJ-1 prevents HFD-induced obesity,insulin resistance and hepatic TG accumulation.However,DJ-1 deficiency had no significant effect on the food intake,liver fatty acid synthesis and glycolysis in mice.Further research found that ablation of DJ-1 accelerate the energy metabolism significantly in mice,And then the fatty acid oxidant and tricarboxylic acid cycle（TCA）of the liver was also significantly increased.Conclusion:Deletion of DJ-1 significantly prevents HFD-induced fatty liver phenotype by promoting hepatic lipid oxidation in the liver.