Effects Of Exercise And Diet Intervention On The FGF21-mTORC1 Pathway In The Liver Of Non-alcoholic Fatty Liver Mice

Objective:Lipid metabolism disorder is the initiating factor of NAFLD induced by obesity.Recently,FGF21 was able to inhibit liver lipid metabolism by mTORC1 through human HepG2 hepatocyte culture.In vivo studies have also confirmed decreased expression of FGF21 protein in the liver of obese mice,but whether it can regulate lipid metabolism through mTOR is not clear.In this study,fatty liver was induced by long-term high-fat diet,and exercise and diet intervention were applied in the development process of NAFLD.To explore the mechanism of NAFLD and the target of exercise and diet intervention in delaying the occurrence of fatty liver.To provide theoretical basis for exploring the methods and means to prevent fatty liver disease.Methods:Male C57BL/6 mice aged 4 weeks were randomly divided into normal group(NC normal diet)and high-fat group(high-fat diet).After 10 weeks,the fat-resistant mice were excluded and the high-fat group was randomly divided into 4 groups: the obesity control group(OBC);Obesity intervention group(OE);Obesity diet intervention group(ODC);Obese exercise diet intervention group(ODE).The diet of the ODC group and the ODE group was 70% of that of the OBC group,and the OE and ODE groups did a 60-minute treadmill six times a week for eight weeks.After the intervention,the liver structure,function,blood lipids,liver free fatty acids and serum FGF21 were detected by immunohistochemistry and ELISA.Real-time PCR and western-blot were used to detect the mRNA transcription level and protein expression level of the FGF21-mTORc1 signaling pathway in liver tissues.Results:1.Compared with the NC group,the body weight,abdominal fat weight,lee’s index,serum TG,TC and ldl-c of mice in the OBC group all increased significantly,while hdl-c decreased significantly.Compared with the OBC group,the body weight,abdominal fat weight,TG,ldl-c and serum of mice in the ODC,OE and ODE groups all decreased significantly,while hdl-c increased significantly.Lee’s index of mice in ODC and ODE groups decreased significantly.2.Pathological sections showed that compared with the NC group,the liver of the OBC group showed obvious fatty degeneration and inflammation;Compared with the OBC group,the degree of hepatic steatosis and inflammation in the ODC,OE,and ODE mice was significantly decreased.3.Compared with NC group,liver index,ALT,AST and FFA of liver homogenate in OBC group were significantly increased.Compared with the OBC group,the above indexes of mice in the ODC,OE and ODE groups all decreased significantly.4.Compared with the NC group,the levels of serum FGF21 and the mRNA levels of liver FGF21,mTOR and S6K1 in the OBC group were significantly increased,but the protein levels of FGF21,β-klotho and TSC2 were significantly decreased,and the relative protein levels of mTOR,p-mtor,S6K1 and p-s6k1 were significantly increased.Compared with the OBC group,the levels of serum FGF21 and the mRNA levels of liver FGF21,mTOR,and mTOR in the ODC,OE,and ODE groups were significantly decreased,protein levels of FGF21,β-klotho,and TSC2 were significantly increased,and relative protein levels of mTOR,p-mtor,S6K1,and p-s6k1 were significantly decreased.Conclusion:1.Long-term high-fat diet can inhibit the fgf21-mtorc1 signaling pathway in the liver,reduce the expression level of FGF21 protein in the liver,weaken the inhibitory effect on the expression of mTOR and S6K1 protein,and lead to hepatic lipid metabolism disorder,which is one of the causes of inducing non-alcoholic fatty liver.2,8 weeks of exercise,diet and combined intervention can alleviate the fgf21-mtorc1 signaling pathway disorders in the liver,improve the lipid metabolism disorders in the liver,and reduce the degree of liver steatosis.3.Exercise and diet intervention have an interactive effect on the prevention and treatment effect of non-alcoholic fatty liver disease,and the combined intervention has a better effect.