Preventive Effect of Ellagic Acid on Cardiac Dysfunction in Diabetic Mice through Regulating DNA Hydroxymethylation

Ellagic acid (EA) improves mitochondrial dysfunction and protects diabetic hearts. The mitochondrial tricarboxylic acid (TCA) cycle regulates DNA 5-hydroxymethylcytosine (5hmC) levels by affecting activity of 10-11 translocation enzymes (TETs). Therefore, we hypothesized that EA prevents diabetic cardiac dysfunction by modulating DNA 5hmC levels. C57BL/6J mice were fed a high-fat diet to induce diabetes and treated with EA (100 mg kg^-1 day^-1) for 8 weeks. Serum concentrations of glucose, insulin, and triglyceride and aspartate transaminase and creatine kinase activities were significantly lower in the EA group than the diabetes mellitus (DM) group. DNA 5hmC levels of mice hearts were significantly higher in the EA group than the DM group. The protein levels of TET, complexes I/III/V were significantly higher in the EA group than the DM group. The results shows that EA has a preventive effect on diabetic cardiac dysfunction, which may be achieved by upregulating TET activity through improving the TCA cycle, to reshape DNA 5hmC levels of mice hearts.