Exercise Improving Cardiac Glycolipid Metabolism in High Fat Diet Induced Type 2 Diabetic Mice through AMPK Pathway

Objective: Diabetes mellitus is an emerging global threat to human health, and impaired myocardial function in diabetic patients is the major pathogenic factor leading to heart failure or sudden death. To test the hypothesis that exercise may protect the heart from metabolic disturbance in type 2 diabetes heart via AMPK, we studied the expression of AMPK and its downstream proteins in high-fat diet (HFD) -induced type 2 diabetic mice with eight weeks aerobic combined with resistance exercise intervention. Methods: The diabetic mice model were induced by HFD for sixteen weeks. After that, diabetes mice were divided into diabetic sedentary group (DS) and diabetic exercise group (DE) randomly. DE group was intervened with eight weeks aerobic combined with aerobic resistance exercise. The intraperitoneal glucose tolerance test (IPGTT) was used to detect glucose tolerance, Sirius red staining was applied to detect fibrosis and wheat germ agglutinin (WGA) staining was used to evaluate myocyte size in heart tissue. Western blot was used to measure the protein level of AMPK pathway. Results: Compared with controls, HFD increased body weight, blood glucose levels in IPGTT in diabetic mice (P<0.01) , heart weight (P<0.05) , heart weight/tibia length (P<0.01) and perivascular fibrosis (P<0.05) . Eight weeks combined exercise program could alleviate compromised glucose tolerance (P<0.01) and decrease perivascular fibrosis (P<0.01) . More importantly, we identified that exercise might alleviate glycolipid metabolic disturbance in HFD-induced diabetic heart via activating AMPK (P<0.01) and its downstream protein, involving upregulation of SIRT1 (P<0.01) , PGC-1 a (P<0.01) and downregulation of PPARa (P<0.01) . Conclusion: The results suggest that eight weeks aerobic combined with resistance exercise could alleviate glycolipid metabolic disturbance and myocardial remodeling in HFD-induced diabetic heart AMPK and its downstream. These data indicated that long-term aerobic combined with resistance exercise might exert a cardiac protective effect against diabetes mellitus and associated cardiomyopathy.