The PI3K/AKT/FoxO3a Signal Transduction Pathways In The Pathogenesis Of Nonalcoholic Fatty Liver Disease

Object:To explore the possible mechanism of the high-fat diet induced non-alcoholic fatty liver disease and observe the Liraglutide in rats induced by high-fat diet whether there is a treatment of nonalcoholic fatty liverMethods:426-week-old male SD rats were randomly divided into normal group(n=18)、control group (n=18) and treatment group (n=6). Normal group and control group were respectively fed with the basal diet and high fat diet, at4weeks,8weeks,12weeks were sacrificed6per batch. Treatment group with high fat diet,9weeks began to be liraglutide intraperitoneal injection (100ug/kg the QD), corresponding to the normal group and the control group received the same amount of normal saline by intraperitoneal injection.Observation index:The body weight of rats, liver wet weight, liver index and serum ALT, AST, TG, TC levels, The degree of hepatic steatosis and hepatic cell apoptosis, expression of hepatic PI3K mRNA, AKT mRNA, FoxO3a mRNA and BimmRNA.Results:1、High fat diet successfully established rat model of non-alcoholic fatty liver:serum ALT, AST, TG, TC levels were significantly higher than those in the normal group, liver histology showed large amounts of liver cell steatosis and ballooning degeneration.2、Body weight, liver wet weight, liver index:The rat body weight, liver wet weight, liver index in control group of three time points were higher than those of the corresponding normal group, P<0.05;and those indications in the treatment group were lower than their corresponding control group, P<0.05.3、Serum ALT, AST, TG, TC levels:The serum level of ALT、 TST、TC、TC in control group of three time points were higher than those of their corresponding normal group, P<0.05;and the serum level of ALT、AST、TG、TC in treatment group were significantly lower than the corresponding control group,P<0.05.4、Hepatocyte apoptosis rate:control group rat hepatocyte apoptosis at three time points were higher than in the corresponding normal group (P<0.05); treatment group hepatocyte apoptosis rate were lower than the corresponding control group, P<0.05.5、The degree of hepatic steatosis:Control group with the prolonged feeding time, the degree of liver fatty degeneration gradually increased,(P<0.05); treatment group and their corresponding control group the indication was no significant difference (P>0.05).6、Expression level of liver PI3K mRNA, AKT mRNA, FoxO3a mRNA, Bim mRNA:The liver tissue PI3K mRNA, AKT mRNA expression levels in the control group at three time points were lower than the corresponding normal group, FoxO3a mRNA, Bim mRNA expression levels were higher than the corresponding normal group,(P<0.05);and the expression levels of liver tissue FoxO3a mRNA、AKT mRNA in the treatment group were higher than the corresponding control group, the expression level of FoxO3amRNA, Bim mRNA were lower than the corresponding control group, P<0.05.Conclusion:1、High fat diet successfully established rat model of nonalcoholic fatty live disease.2、Apoptosis and fatty degeneration of the liver, is the main pathological changes of NAFLD rats. In the pathogenesis of NAFLD rats have PI3K/AKT/FoxO3a signaling pathway exists.3、High-fat diet-induced NAFLD may be through inhibition of rat liver tissue expression of PI3K and AKT, increase non-phosphorylated FoxO3a and increased expression of Bim, promote hepatic steatosis and hepatic apoptosis.4、Liraglutide in rats with nonalcoholic fatty liver have a therapeutic effect, the mechanism may influence PI3K/AKT/Fox03a pathway, inhibition of hepatic apoptosis.