Protective Effects And Mechanisms Of Liraglutide On The Macrovascular Lesions Of Rats Fed With High Fat Diet

Objective: To investigate the protective effects and mechanism of GLP-1analogueliraglutide on macrovascular lesions of rats fed with high fat diet.Methods: Sixty clean male SD rats were randomly divided into four groupsaccording to body weight. They were respectively fed with normal diet (ND), high fatdiet (HFD), high fat diet with low doses of liraglutide injected hypodermically(HFD+LLID), high fat diet with high doses of liraglutide injected hypodermically(HFD+HLID).After12weeks, the body weight, abdominal aortic intima-mediathickness（IMT）under the four-dimensional ultrasound, fasting blood sugar，lipidprofile, HOMA-IR level were measured, the change of PGC-1a gene and proteinexpression level in liver were detected by PCR, immunohistochemistry and Westernbloting.Results: Compared with those in ND group, the body weight, IMT, fasting bloodsugar，lipid profile, HOMA-IR level of HFD group increased significantly, PGC-1agene and protein expression level in liver decreased significantly(P<0.05).Comparedwith the HFD group, there were significantly higher for the body weight, IMT,fasting blood sugar，lipid profile, HOMA-IR level and significantly lower for PGC-1agene and protein expression level in liver of HFD+LLID,HFD+HLID(P<0.05).Butthe effect of HFD+HLID was most pronounced.Conclusions:1、Liraglutide can increase the expression of the PGC-1a in liver.2、The macrovascular lesions induced by high fat diet can be protected by Liraglutide,and its protective effect is dose-dependent.3、The protective effect of Liraglutide onmacrovascular lesions which induced by high fat diet may have a relationship with theimprovement of lipid profile which relate to an increase of the PGC-1a expression level in liver.