Metabolic Remodeling Induced by Exercise: Emerging Mechanisms for Myocardial Protection in Cardiovascular Disease

Cardiovascular diseases (CVDs), including coronary artery disease, heart failure, arrhythmias, hypertension, and cardiomyopathy, promote disease progression in part through profound disturbances in cardiomyocyte metabolism. These disorders are characterized by abnormal lipid and glucose metabolism and dysfunction of key metabolic regulatory systems, including fatty acid transport proteins and the AMPK/eNOS signaling axis. Exercise training regulates substrate selection and activates essential metabolic pathways, including PGC-1α and PPAR-α, thereby improving myocardial energy homeostasis and limiting cardiac injury. This review summarizes the mechanisms by which exercise modulates myocardial metabolism to delay or reverse disease progression across multiple forms of CVDs. Current evidence indicates that distinct cardiovascular pathologies exhibit unique metabolic abnormalities, suggesting that exercise interventions may exert disease-specific therapeutic effects by selectively targeting altered metabolic pathways.