the ppar-pgc-1 axis controls cardiac energy metabolism in healthy and diseased myocardiumppar-pgc-1轴控制心脏健康和病变心肌能量代谢.pdfVIP

Hindawi Publishing Corporation PPAR Research Volume 2008, Article ID 253817, 10 pages doi:10.1155/2008/253817 Review Article The PPARα-PGC-1α Axis Controls Cardiac Energy Metabolism in Healthy and Diseased Myocardium Jennifer G. Duncan and Brian N. Finck 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 Correspondence should be addressed to Brian N. Finck, bfinck@ Received 16 July 2007; Accepted 3 September 2007 Recommended by Giulia Chinetti 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 PPARα and its cardiac-enriched coactivator protein, PGC-1α, play impor- tant roles in the transcriptional control of myocardial energy metabolism. The PPARα-PGC-1α 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 PPARα-PGC-1α 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 PPARα-PGC-1α axis in regulating mitochondrial energy metabolism and cardiac function in response to physiologic and pathophysiologic stimuli. Copyright © 2008 J. G. Duncan and B. N. Finck. This is an open access article distributed under the Creative Commons Attribution License, wh