The role of myocardial energy metabolism perturbations in diabetic cardiomyopathy: from the perspective of novel protein post-translational modifications

Abstract Diabetic cardiomyopathy (DbCM), a significant chronic complication of diabetes, manifests as myocardial hypertrophy, fibrosis, and other pathological alterations that substantially impact cardiac function and elevate the risk of cardiovascular diseases and patient mortality. Myocardial energy metabolism disturbances in DbCM, encompassing glucose, fatty acid, ketone body and lactate metabolism, are crucial factors that contribute to the progression of DbCM. In recent years, novel protein post-translational modifications (PTMs) such as lactylation, β-hydroxybutyrylation, and succinylation have been demonstrated to be intimately associated with the myocardial energy metabolism process, and in conjunction with acetylation, they participate in the regulation of protein activity and gene expression activity in cardiomyocytes. This review examines the epigenetic pathogenesis of DbCM, primarily focusing on myocardial energy metabolism perturbations and novel PTMs associated with them. It provides a detailed analysis of the mechanisms of these novel PTMs in DbCM to enhance the understanding of DbCM pathophysiology and establish a theoretical foundation for the development of new treatment strategies for DbCM.