Nuclear receptor signaling and cardiac energetics.
The heart has a tremendous capacity for ATP generation, allowing it to function as an efficient pump throughout the life of the organism. The adult myocardium uses either fatty acid or glucose oxidation as its main energy source. Under normal conditions, the adult heart derives most of its energy through oxidation of fatty acids in mitochondria. However, the myocardium has a remarkable ability to switch between carbohydrate and fat fuel sources so that ATP production is maintained at a constant rate in diverse physiological and dietary conditions. This fuel selection flexibility is important for normal cardiac function. Although cardiac energy conversion capacity and metabolic flux is modulated at many levels, an important mechanism of regulation occurs at the level of gene expression. The expression of genes involved in multiple energy transduction pathways is dynamically regulated in response to developmental, physiological, and pathophysiological cues. This review is focused on gene transcription pathways involved in short- and long-term regulation of myocardial energy metabolism. Much of our knowledge about cardiac metabolic regulation comes from studies focused on mitochondrial fatty acid oxidation. The genes involved in this key energy metabolic pathway are transcriptionally regulated by members of the nuclear receptor superfamily, specifically the fatty acid-activated peroxisome proliferator-activated receptors (PPARs) and the nuclear receptor coactivator, PPARgamma coactivator-1alpha (PGC-1alpha). The dynamic regulation of the cardiac PPAR/PGC-1 complex in accordance with physiological and pathophysiological states will be described.
Huss
Janice M
JM
Center for Cardiovascular Research and Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Kelly
Daniel P
DP
D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D006332:Cardiomegaly / Q000378:metabolism; D048909:Diabetes Complications / Q000378:metabolism; D004734:Energy Metabolism; D005227:Fatty Acids / Q000378:metabolism; D005544:Forecasting; D005947:Glucose / Q000378:metabolism; D006333:Heart Failure / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000502:physiology; D006801:Humans; D051379:Mice; D008929:Mitochondria, Heart / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D047492:Peroxisome Proliferator-Activated Receptors / Q000502:physiology; D017434:Protein Structure, Tertiary; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / Q000502:physiology*; D011960:Receptors, Estrogen / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology; D000097983:ERRalpha Estrogen-Related Receptor
D000255:Adenosine Triphosphate; D005227:Fatty Acids; D005947:Glucose; D006360:Heat-Shock Proteins; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D047492:Peroxisome Proliferator-Activated Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D011960:Receptors, Estrogen; D014157:Transcription Factors; D000097983:ERRalpha Estrogen-Related Receptor; C486497:PPARGC1A protein, human