Effects And Mechanisms Of Cardiomyocyte Specific Over Expression Of Acyl-coA Thioesterase 1 On Diabetic Heart

Objective: To investigate the role of Acyl-co A Thioesterase 1(ACOT1) in the process of diabetic cardiomyopathy and the involved mechanism.Methods: In order to explore the effect of ACOT1 in diabetic heart, we constructed the cardiomyocyte specific over expression of ACOT1 transgenic mice. Both the 4 weeks old transgenic mice and their littermates control mice were fed by the high fat die and normal diet for 20 weeks. Body weight and blood glucose were monitored every two weeks. At the end of the 20 th week, heart function and the cardiac structure were assessed by echocardiography and in vivo hemodynamic tests. Then the status of glucose and fatty acid metabolism were showed by assessing the expression of genes involved in glucose and fatty acid metabolic pathway through western blot and real-time PCR.Results: High fat diet induced diabetic cardiomyopathy evidenced by cardiac dysfunction, cardiac hypertrophy and myocardial fibrosis, which could be attenuated by cardiomyocytespecific over expression of ACOT1. We also confirmed that in diabetic hearts glucose metabolism were inhibited while over expression of ACOT1 could increase the glucose utilization through protein kinases B and glucose transporter type 4(p AKT/GLUT4) pathway. Additionally, in the hearts of ACOT1 transgenic mice the lipids storage was decreased, compared with their littermates control mice. Interestingly, the peroxisome proliferatoractivated receptor alpha and PPAR co-activator 1a(PPARa/PGC1a) signaling, which was over activated during diabetic was repressed by the over expression of ACOT1.Conclusion: Cardiomyocyte specific over expression of ACOT1 improves cardiac function which is suppressed during diabetic through the modification of glucose metabolism and fatty acid oxidation.