Effect of GLP-1 on insulin resistance and PKCεin rats with nonalcoholic fatty liver disease induced by high fat diet / 中国病理生理杂志

ABSTRACT

AIM:To observe the therapeutic effect of glucagon-like peptide 1 (GLP-1) analog on nonalcoholic fatty liver disease of rats and to investigate the underlying mechanism.METHODS:SD rats (n=21) were used to estab-lish a nonalcoholic fatty liver disease model by feeding a high fat diet for 12 weeks, and other 11 rats were fed with a normal diet for 16 weeks.The model rats were randomly divided into 2 equal groupsone group was treated with glucagon-like pep-tide 1 analog (0.6 mg· kg-1 · d-1 ) by intraperitoneal injection for 4 weeks, the other group using saline as a control.Af-ter treatment, fasting blood glucose, serum insulin, blood lipids, liver function and the pathological changes of the hepatic tissues were evaluated and the expression of PKCεat mRNA and protein levels in the liver tissues was detected by real-time PCR and Western blot, respectively.RESULTS:Compared with model group, the intervention of GLP-1 significantly re-duced insulin resistance index (HOMA-IR), improved the liver function (P<0.05), decreased the liver index and blood lipids (P<0.05).HE staining showed obvious pathological changes of the hepatic tissues in model group, and the inter-vention of GLP-1 significantly reduced lipid droplets in the hepatocytes and improved the structural damage of the liver.The expression of hepatic protein kinase Cε( PKCε) at mRNA and protein levels significantly decreased which were reversed by treating with GLP-1.CONCLUSION:GLP-1 shows good therapeutic effect on nonalcoholic fatty liver disease of rats, pos-sibly by controlling lipid metabolism and reducing insulin resistance, which may be related to PKCεexpression.