Regulatory Networks Controlling Mitochondrial Energy Production in the Developing, Hypertrophied, and Diabetic Heart

The adult mammalian heart is highly specialized for efficient and high-capacity energy production to meet thediverse physiologic demands of the postnatal environment. In contrast to the fetal heart, which relies largely onglucose, the adult heart is programmed to rely on multiple energy sources. Although the postnatal heart continues to utilize glucose, the primary source of ATP is themitochondrial fatty acid oxidation (FAO) pathway (Bing1955; Neely et al. 1972; Schulz 1991). The expression ofFAO pathway enzymes is induced following birth via developmentally programmed nuclear gene regulatoryevents. The relative importance of glucose and fatty acidsas fuel sources for the adult heart is a function of developmental, physiologic, and dietary contexts (Lockwoodand Bailey 1970; Neely et al. 1972; Schulz 1991). For example, energy production in the fetal heart is primarilyvia glycolysis because mitochondrial oxidative capacityis limited. Furthermore, although the energy demands ofthe fully developed heart are mainly met by the oxidationof fats, glucose utilization is important in postprandialstates and with sudden increases in hemodynamic load.Thus, the normal adult heart exhibits "plasticity" in its energy substrate choices...