2026-10-14T04:26:11Z https://www.scidb.cn/oai

10.57760/sciencedb.35406 2026-07-09T10:52:15Z

2026-07-09 N-3 polyunsaturated fatty acids prevent diabetic cardiomyopathy by promoting TET2-mediated DNA demethylation doi:10.57760/sciencedb.35406 en Diabetes cardiomyopathy (DCM) has become an important complication of diabetes, and its pathogenesis is closely related to the disorder of active DNA methylation. N-3 polyunsaturated fatty acids (n-3 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 DCM, DCM mice were then divided into four groups: 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 group (CON) was fed with a standard diet (normal saline). Fasting serum concentrations of insulin, TC, TG, LDL-C, and the atherogenic index of plasma were significantly lower in both Ln-3 and Hn-3 groups than in DCM group. Total n-3 PUFAs and n-3/n-6 n-3 PUFAs ratio in heart were significantly lower in DCM group than them in CON, Ln-3 and Hn-3 groups. N-3 PUFAs improved cardiac contractile and diastolic functions, reduced cardiomyocyte hypertrophy and fibrosis, and enhanced cardiac function of mice. The protein expression levels of TET2 and p-AMPKα/AMPKα in mice heart of Hn-3 group were significantly higher than those in DCM group. The ratio of α-ketoglutarate to (succinate + fumarate) in DCM group was significantly lower than that in 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. Run Liu EMBARGO https://creativecommons.org/licenses/by-nc-nd/4.0/ dataset Science Data Bank