Melatonin as a prospective metabolic regulator in pathologically altered cardiac energy homeostasis

Abstract

A constant energy supply is indispensable for the relentlessly working heart. The unique metabolic flexibility of the cardiac tissue enables it to maintain its energy requirement under variable physiological conditions. However, some physiopathological statuses including aging, ischemia-reperfusion injury, diabetic cardiomyopathy, pathological cardiac hypertrophy, and heart failure frequently cause cardiac dysfunction and detrimental metabolic alteration. If the ATP supply fails to match the requirement of a working heart, the heart loses its functional capacity, resulting in slower recovery. A decrease in energy generation is often the ramifications of myocardial mitochondrial dysfunction and oxidative stress. Melatonin, a broad-spectrum antioxidant molecule has an appreciable role in the maintenance of metabolic homeostasis― from a single cell to an entire organism. Melatonin has the capacity to reduce ROS generation, preserve mitochondrial stability, and restore a robust mitochondrial function for unabated ATP production in cardiac tissues. Additionally, melatonin can promote carbohydrate and fat metabolism to further improve the ATP production in heart. In cardiac cells, melatonin upregulates GLUT4 expression either by impeding oxidative stress or by enhancing AMPK activation which accelerates fatty acid oxidation by upregulating PPAR-α and CPT-1α. Melatonin plays a pivotal role in the maintenance of calcium homeostasis in cardiomyocytes by obviating oxidative stress-mediated disruption of SERCA and NCX proteins. A possible role of melatonin to convert the Warburg effect to oxidative metabolism in pathological cardiac events has been recently contemplated. The current review will discuss the possible role of melatonin protecting against cardiac metabolic imbalances under pathological states.