Thinned young apple polyphenol prevents diabetic cardiomyopathy through promoting TET2-mediated active DNA demethylation in STZ-induced diabetic mice heart

Diabetic cardiomyopathy (DCM) refers diabetic patients develop cardiomyopathy characterized by cardiac systolic and diastolic dysfunction. Currently, no research has explored the role of ten-eleven translocation (TET)-mediated active DNA demethylation in the development of DCM. Through case-control study, we found that the level of 5-hydroxymethylcystein in peripheral blood DNA of DCM patients was significantly lower than it in the healthy subjects and diabetic patients. Secondly, we had conducted an animal study to explore the effect of thinned young apple polyphenol (TYAP) on DNA demethylation in streptococci-induced diabetic mice. TYAP effectively prevented the ventricular dysfunction and cardiomycyte disarray via alleviating DNA epigenetic modifications metabolic disorders in diabetic mice heart. TYAP increased the stability of TET2 protein via activating phosphorylate AMPK and enhanced the activity of TETs enzymes via improving tricarboxylic acid cycle, then promoted TET-mediated active DNA demethylation. TYAP prevented the occurrence of DCM by promoting TET2-mediated active DNA demethylation in the heart of diabetic mice.