Effects Of Liraglutide On Nonalcoholic Fatty Liver And The Expression Of FGF21 And FoxA2

Objective:With the improvement of people's living standards,non-alcoholic fatty liver disease(NAFLD)has become one of the major chronic diseases that affect human health.It has been shown that the pathogenesis of NALFD is closely related to insulin resistance and abnormal lipid metabolism.Further study of its pathological mechanism is of great significance for the early diagnosis and treatment of fatty liver.In this experiment,a high-fat diet was used to establish a rat model of NAFLD.The biochemical indexes and histopathological changes of liver in each group were observed at various periods,and the expression of FGF21 and FoxA2 in liver was detected,to investigate the effect of liraglutide on NAFLD and the expression of FGF21 and FoxA2.Method:Thirty-five rats were randomly divided into two groups.20 rats were given high-fat diet to establish the NAFLD model as the experimental group,and 15 rats were given normal food as the blank control group.Five rats in each group were sacrificed at week 5 and week 10,respectively,to observe the changes of liver pathology,liver indexes and serum biochemical indexes(lipids,transaminases).After week 10,the remaining 10 rats in the experimental group were randomly divided into 2 groups:one group was injected subcutaneously with liraglutide as the liraglutide group,and one group was subcutaneously injected with the same amount of saline as the model control group.The remaining 5 rats in the blank control group were also injected subcutaneously with an equal amount of physiological saline.After 5 weeks,all remaining three groups of rats were sacrificed.The serum and liver tissue specimens were harvested,for detection of the changes of liver index,liver histopathology and serum biochemical indexes.Also,the expression of FGF21 and FoxA2 in rat liver tissue was analyzed by RT-PCR and Western blot at mRNA and protein level,respectively.Results:1.In the NAFLD model group,blood lipid,transaminase and liver index increased at week 5,10 and 15 compared to that of the blank control group(P<0.05 or P<0.01).However,after liraglutide treatment,the serum lipids,transaminase and liver index of NAFLD rats decreased(P<0.05).2.For the livers of blank control group,no significant abnormality was observed during the three periods.Compared to that of the blank control group of the corresponding period,the liver of model group was significantly larger,more hardened,brittle,and yellowish color.The above changes were more pronounced as modeling time became longer.After liraglutide treatment,the liver morphology,texture,and color of NAFLD rats were improved.3.By observation of liver specimens under light microscope and NAS score,no obvious steatosis was found in the hepatocytes of the blank control rats.To the contrary,hepatocyte steatosis was observed in the NAFLD model group rats,and the NAS score was increased compared to the blank control group(P<0.01).After liraglutide treatment,the liver NAS score of NAFLD rats was decreased(P<0.05).4.RT-PCR results showed that the mRNA expression of FGF21 and FoxA2 in the model group was significantly upregulated compared to the blank control group(P<0.01),and the expression of FGF21 and FoxA2 mRNA was decreased after the administration of liraglutide compared to the model group(P<0.01).5.Western blot results showed that compared to the blank control group,the expression of FGF21 and FoxA2 protein in the model group was increased(P<0.01),and the protein expression of FGF21 and FoxA2 was decreased after the administration of liraglutide compared to the model group(P<0.05 or P<0.01).Conclusion1.82.5%normal maintenance feed + 15%lard + 0.5%bile salt + 2%cholesterol is a diet to effectively establish a NAFLD model in SD rat.2.Liraglutide treatment significantly alleviates liver inflammation and steatosis in NAFLD rats,and have protective effect on NAFLD liver.3.The upregulation of FGF21 and FoxA2 expression in the liver of NAFLD rats is likely a protective mechanism of NAFLD.4.Liraglutide treatment improves NAFLD by regulating the expression of FGF21 and FoxA2 in the liver.