Integrative insights into fatty acid metabolism in diabetic cardiomyopathy: From molecular mechanisms to therapeutic strategies

Diabetic cardiomyopathy (DCM) is a diabetes-specific cardiac dysfunction independent of other cardiovascular diseases. Recent studies highlight dysregulated fatty acid (FA) metabolism as a central driver of its pathogenesis. In the diabetic heart, excessive FA uptake and oxidation imbalance with glucose utilization led to lipid accumulation, mitochondrial overload, and oxidative stress. These changes trigger inflammatory responses, impair mitochondrial structural integrity and quality control, and disrupt cellular energy homeostasis. Over time, this maladaptation promotes cardiomyocyte hypertrophy, interstitial fibrosis, and progressive diastolic dysfunction. This review synthesizes current knowledge on the links between FA metabolic dysregulation and DCM, from metabolic overload to structural remodeling. It also discusses emerging therapeutic strategies aimed at reducing pathological lipid influx, optimizing energy substrate balance, restoring mitochondrial function, and preventing downstream injury, with the goal of guiding precision interventions for DCM.