These changes in energysubstrate preference are mediated, at least in part, by a downregulation of thegenes encoding enzymes involved in FAO, OXPHOS, and the PPARα-PGC-1α complex [3, 48, 51–60].The expression of the genes encoding PPARα and PGC-1α is known to be diminished in severalrodent models of pressure overload or hypertensive heart disease [3, 40, 61], pacing-induced heart failure [62, 63], hypoxia [52], ischemic heart disease [55, 58, 59, 64], as well as genetically engineered models of heart failure [65–67]. The gene discussed is PPARGC1A; the disease is heart failure.