The Gift of Light

Abstract

Heart failure (HF) resulting from impaired left ventricular (LV) function is associated with significant morbidity and mortality in the United States and worldwide.1 In the failing heart, there are changes in energy substrate metabolism whose causes and effects are poorly understood.2 These changes may contribute to deterioration in cardiac contractility and to increasing LV remodeling that are the hallmarks of the failing heart. In HF following cardiac hypertrophy, there is a major metabolic switch in myocardial substrate metabolism from fatty acid to glucose oxidation.2–5 A key marker of this switch is the coordinated downregulation of fatty acid oxidation enzymes (eg, medium-chain acyl-CoA dehydrogenase and carnitine palmitoyltransferase-I β) and mRNA levels in the human LV with a concomitant increase in glucose uptake and oxidation.2,6 This switch is thought to represent a metabolic reprogramming toward substrate metabolism that is more commonly seen in the fetal heart.7 The fetus in a womb uses glucose from the mother as the major substrate for energy production; in fact, ≈80% of fetal energy comes from glucose oxidation. See Article by Panagia et al Moreover, recent studies have suggested that brown adipose tissue (BAT) may play an important role in obesity, type 2 diabetes mellitus, and HF.8–13 BAT regulates basal and inducible energy expenditure in humans and is composed of cells that contain numerous lipid droplets, dense packing of mitochondria, and the expression of the mitochondria-associated UCP1 (uncoupling protein 1).11 UCP1 mediates the biochemical uncoupling of electron transport by allowing proton leakage across the inner mitochondrial membrane into the mitochondrial matrix, thus short-circuiting the usual linkage of electron transport to adenosine triphosphate production that is catalyzed by ATP synthase.11 Instead, the chemical energy generated by cellular respiration in brown adipocytes is dissipated in …