Transcriptional Activation Of Energy Metabolic Switches In The Developing And Hypertrophied Heart

作者：John J. Lehman, Daniel P. Kelly · 发表于：Clinical and Experimental Pharmacology and Physiology · 年份：2002 · DOI：10.1046/j.1440-1681.2002.03655.x · 被引用次数：262 · 研究领域：Peroxisome Proliferator-Activated Receptors、Adipose Tissue and Metabolism、Mitochondrial Function and Pathology

1. The present review focuses on the gene regulatory mechanisms involved in the control of cardiac mitochondrial energy production in the developing heart and following the onset of pathological cardiac hypertrophy. Particular emphasis has been given to the mitochondrial fatty acid oxidation (FAO) pathway and its control by members of the nuclear receptor transcription factor superfamily. 2. During perinatal cardiac development, the heart undergoes a switch in energy substrate preference from glucose in the fetal period to fatty acids following birth. This energy metabolic switch is paralleled by changes in the expression of the enzymes and protein involved in the respective pathways. 3. The postnatal activation of the mitochondrial energy production pathway involves the induced expression of nuclear genes encoding FAO enzymes, as well as other proteins important in mitochondrial energy transduction/production pathways. Recent evidence indicates that this postnatal gene regulatory effect involves the actions of the nuclear receptor peroxisome proliferator-activated receptor alpha (PPARalpha) and its coactivator the PPARgamma coactivator 1 (PGC-1). 4. The PGC-1 not only activates PPARalpha to induce FAO pathway enzymes in the postnatal heart, but it also plays a pivotal role in the control of cardiac mitochondrial number and function. Thus, PGC-1 plays a master regulatory role in the high-capacity mitochondrial energy production system in the adult mammalian heart. 5. During t...