The PPARalpha-PGC-1alpha Axis Controls Cardiac Energy Metabolism in Healthy and Diseased Myocardium.
The mammalian myocardium is an omnivorous organ that relies on multiple substrates in order to fulfill its tremendous energy demands. Cardiac energy metabolism preference is regulated at several critical points, including at the level of gene transcription. Emerging evidence indicates that the nuclear receptor PPARalpha and its cardiac-enriched coactivator protein, PGC-1alpha, play important roles in the transcriptional control of myocardial energy metabolism. The PPARalpha-PGC-1alpha complex controls the expression of genes encoding enzymes involved in cardiac fatty acid and glucose metabolism as well as mitochondrial biogenesis. Also, evidence has emerged that the activity of the PPARalpha-PGC-1alpha complex is perturbed in several pathophysiologic conditions and that altered activity of this pathway may play a role in cardiomyopathic remodeling. In this review, we detail the current understanding of the effects of the PPARalpha-PGC-1alpha axis in regulating mitochondrial energy metabolism and cardiac function in response to physiologic and pathophysiologic stimuli.
Duncan
Jennifer G
JG
Center for Cardiovascular Research, Departments of Pediatrics and Medicine, Washington University School of Medicine, 660 S. Euclid Avenue Campus Box 8031, Saint Louis, MO 63110, USA.
Finck
Brian N
BN