The Effects Of AMPK?2 Deficiency In Diabetic Cardiomyopathy Mice After 8 Weeks Exercise Intervention

Objective: To test the hypothesis that exercise may protect the heart from diabetic cardiomyopathy(DCM)via AMPK?2,we studied the expression of AMPK and its downstream proteins in high-fat diet(HFD)-induced diabetic cardiomyopathy,and analyzed the function of AMPK?2 in DCM after eight weeks aerobic combined with resistance exercise intervention.Methods: In part one,the eight-weeks C57 mice were randomly divided into low fat diet(LFD)sedentary group(WT+NS)and HFD sedentary group(WT+DS),and KO mice were randomly divided into LFD sedentary group(KO+NS)and HFD sedentary group(KO+DS).We tested the fasting blood glucose to select the mice in fifteen and sixteen weeks.In part two,the eight-weeks WT mice were randomly divided into sedentary group(WT+DS)and exercise group(WT+DE),and AMPK?2 KO mice were randomly divided into sedentary group(KO+DS)and exercise group(KO+DE).Testing the fasting blood glucose to select the mice in fifteen and sixteen weeks,mice were intervened with eight weeks aerobic combined with aerobic resistance exercise in DE group.After twenty-four weeks,the intraperitoneal glucose tolerance test(IPGTT)was used to detect glucose tolerance,Sirius red staining and wheat germ agglutinin staining was used.Western blot was used to measure the protein level of AMPK and its downstream proteins.Results: After 24 weeks of HFD,mice developed impaired glucose tolerance,myocardial diastolic function,and myocardial remodeling,which indicated that HFD-induced DCM model was successfully established.AMPK?2 KO did not affected the indexes in NS group.But AMPK?2 KO aggravated the HFD-induced hyperlipemia impaired myocardial function,myocardial interstitial fibrosis and cardiac hypertrophy,as well as downregulation of p-AS160 Thr642/AS160,GLUT4,SIRT1,PGC1-?,ERR? and CPT1 b,upregulation of PPAR?,CD36 and C/EBP? in the heart of DCM mice.AMPK?2 KO have no effects on the HFD-induced downregulation of p-GSK3?Ser9/GSK3? and MCAD in heart(P<0.05).Exercise alleviated HFD-induced hyperlipemia,myocardial fibrosis and cardiac myocyte size (P<0.05),decrease of HDL-C(P<0.05),upregulation of CD36,PPAR?,MG53 and C/EBP?(P<0.05),downregulation of p-GSK3?Ser9/GSK3?,SIRT1 and PGC1-?,at least partial dependent of AMPK?2(P<0.05).Conclusion: AMPK?2 plays an important role in the regulation of serum lipid levels,myocardial glucose transport,mitochondrial transcription factor,fatty acid uptake and oxidation,and cardiac structural function,but maybe not related to glycogen synthesis in DCM heart.Exercise regulates lipid levels,as well as glycogen synthesis,mitochondrial transcription factors,fatty acid uptake and oxidation,and myocardial function in DCM heart at least partially dependent on AMPK?2,but the regulation of myocardial glucose transport maybe not related to AMPK?2.