2026-10-13T09:07:23Z https://www.scidb.cn/oai

10.57760/sciencedb.19594 2025-01-16T17:07:22Z

2025-01-16 N-3 polyunsaturated fatty acids prevent diabetic cardiomyopathy by promoting TET2-mediated DNA demethylation doi:10.57760/sciencedb.19594 en Diabetes cardiomyopathy (DCM) has become an important complication of diabetes, and its pathogenesis is closely related to the disorder of active DNA methylation. 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. The left ventricular mass index (LV mass index) and left ventricular posterior wall thickness in systole (LVPW; s) were significantly lower in CON, Ln-3 and Hn-3 groups than in DCM group. The protein expression levels of TET2 and p-AMPKα/ AMPKα in mice heart of the Hn-3 group were significantly higher than those in the DCM group. The ratio of α-ketoglutarate to (succinate + fumarate) in the DCM group was significantly lower than that in the Ln-3 and Hn-3 groups. In conclusion, n-3 PUFAs prevented the occurrence of DCM by promoting TET2-mediated DNA demethylation in diabetic mice heart. N-3 polyunsaturated fatty acids; Diabetic cardiomyopathy; Ten-eleven translocation 2; Active DNA demethylation; Tricarboxylic acid cycle. 刘润 PUBLIC https://creativecommons.org/licenses/by-nc/4.0/ dataset Science Data Bank