Brown adipose tissue: a potential therapeutic target for preventing cardiovascular disease in metabolic disorders

Abstract Background Obesity and Type 2 diabetes (T2D) remain significant health challenges contributing to cardiovascular complications. This study aimed to investigate brown adipose tissue (BAT) and connexin43 (Cx43) in obese T2D rats and evaluate the effects of antioxidant Cemtirestat. Cx43 plays a crucial role in both BAT and heart function, yet its expression in T2D hearts remains underexplored. Materials and methods Forty male Zucker diabetic fatty (ZDF) rats were divided into four groups: (1) lean nondiabetic (ZDF lean), (2) Cemtirestat-treated lean nondiabetic (ZDF lean + C), (3) obese diabetic (ZDF T2D), and (4) Cemtirestat-treated obese diabetic (ZDF T2D + C). After 6 months, biometric and biochemical parameters were measured and Cx43, selected protein kinases and batokines were analyzed in the BAT and left ventricle. Echocardiograms were recorded prior to study completion. Results Obese T2D rats exhibited increased body weight, heart weight, visceral fat, BAT mass, glucose, insulin, cholesterol and triglycerides. Cx43 was decreased in BAT but increased in the left ventricles of T2D rats. Cemtirestat increased Cx43 in BAT of lean rats but not in the left ventricles of obese T2D rats. Protein kinase C epsilon was reduced in BAT, while protein kinase C delta was increased in both BAT and left ventricles of T2D rats and partially normalized by Cemtirestat. BAT whitening together with reduced mitochondrial uncoupling protein 1 and fibroblast growth factor 21 were observed in T2D rats. Echocardiography revealed diastolic dysfunction in T2D rats, which was attenuated by Cemtirestat. Conclusion These findings support the role of BAT as a therapeutic target in metabolic disease and identify Cx43 as a molecular mediator linking adipose tissue dysfunction to cardiac impairment. Although low-dose Cemtirestat showed limited efficacy, it demonstrates potential for cardiometabolic intervention, justifying further investigation. Graphical Abstract