Autophagy, Metabolic Disease, and Pathogenesis of Heart Dysfunction

Abstract In normal physiology, autophagy is recognized as a protective housekeeping mechanism that enables elimination of unhealthy organelles, protein aggregates, and invading pathogens, as well as recycling cell components and producing new building blocks and energy for cellular renovation and homeostasis. However, overactive or depressed autophagy is often associated with the pathogenesis of multiple disorders, including cardiac disease. During metabolic disorders, such as diabetes and obesity, dysregulation of autophagy frequently leads to cell death, cardiomyopathy, and cardiac dysfunction. In this article, we summarize the current understanding of autophagy—its classification, progression, and regulation; its roles in both physiological and pathophysiological conditions; and the balance between autophagy and apoptosis. We also explore how dysregulation of autophagy leads to cell death in models of metabolic disease and its contributing factors—including nutrient state, hyperglycemia, dyslipidemia, insulin inefficiency, and oxidative stress—and outline some recent efforts to restore normal autophagy in pathophysiological states. This information could provide potential targets for the prevention of, or intervention in, cardiac failure in metabolic disorders such as diabetes and obesity.