Peroxisome proliferator-activated receptor α (PPARα) signaling in the gene regulatory control of energy metabolism in the normal and diseased heart

被引:135
作者
Finck, BN
Kelly, DP
机构
[1] Washington Univ, Sch Med, Cardiovasc Res Ctr, Dept Med, St Louis, MO 63110 USA
[2] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA
[3] Washington Univ, Sch Med, Dept Mol Biol & Pharmacol, St Louis, MO 63110 USA
关键词
D O I
10.1006/jmcc.2002.2061
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The tremendous energy demands of the post-natal mammalian heart are fulfilled via dynamic flux through mitochondrial oxidative pathways. The capacity for energy production via fatty acid (FA) beta-oxidation pathway is determined, in part, by the regulated expression of genes encoding FA utilization enzymes and varies in accordance with diverse dietary and physiologic conditions. For example, fasting and diabetes activate the expression of cardiac FA oxidation (FAO). Peroxisome proliferator-activated receptor alpha (PPARalpha) is a ligand-activated transcription factor that is known to control the expression of many genes involved in cellular FA import and oxidation. Cardiac FA utilization rates are reduced in PPARalpha null mice due to diminished expression of genes encoding FAO enzymes. Recent work has shown that the PPARalpha regulatory pathway is deactivated in pathologic cardiac hypertrophy and hypoxia, two circumstances characterized by reduced FAO and increased dependence on glucose as a fuel source. Conversely, the activity of the PPARalpha gene regulatory pathway is increased in the diabetic heart, which relies primarily on FAO for energy production. In fact, evidence is emerging that excessive FA import and oxidation may be a cause of pathologic cardiac remodeling in the diabetic heart. This review summarizes the regulation of cardiac substrate utilization pathways via the PPARalpha complex in the normal and diseased heart. (C) 2002 Published by Elsevier Science Ltd.
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页码:1249 / 1257
页数:9
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