N-3 polyunsaturated fatty acids prevent diabetic cardiomyopathy by promoting TET2-mediated DNA demethylation

It has been reported that n-3 polyunsaturated fatty acids (PUFAs) improved insulin resistance and cardiovascular function, however the underlay molecular mechanism is unknown. The mice were fed with high-fat diet and injected with STZ (55mg/kg/d) for 7 consecutive days.

Diabetes mice were fed with high-fat diet for another 12 weeks to induce diabetes cardiomyopathy (DCM), DCM mice were then divided into four groups (n=15): DCM group (normal saline); metformin group (MET, 150 mg/kg/d metformin buffer); low-dose n-3 PUFAs group (Ln-3, 150 mg/kg/d); high-dose n-3 PUFAs group (Hn-3, 300 mg/kg/d). The control (CON) group was fed with a standard diet (normal saline). Fasting serum concentrations of insulin, total cholesterol (TC), triglycerides (TG), low-density lipoprotein levels (LDL-C), and the atherogenic index of plasma (AIP) were significantly lower in both Ln-3 and Hn-3 groups than in DCM group. Total n-3 PUFAs and n-3/n-6 ratio in heart were significantly lower in DCM group than in CON, Ln-3 and Hn-3 groups. The ejection fraction (EF), fractional shortening (FS), early diastolic mitral annular velocity (E’/A’) were significantly lower in DCM group than in CON and Hn-3 groups.