Deranged energy substrate metabolism in the failing heart.
Control of energy metabolism in the heart is closely linked to cardiac performance. Dysregulation of energy-generating pathways occurs in many forms of heart disease, including heart failure. Uncertainty exists as to whether these alterations in the way adenosine triphosphate (ATP) is produced serve to protect the heart from excessive oxygen demands or have untoward long-term consequences. Regulation of fatty acid beta-oxidation (FAO), the principal source of ATP in the healthy heart, occurs at multiple levels, including a strong gene transcriptional component. In the heart, members of the peroxisome proliferator-activated receptor (PPAR) family of transcription factors are the primary regulators of FAO gene expression. PPARs are ligand activated by endogenous lipids and synthetic small molecules, thus providing attractive targets for pharmaceutical intervention. This article discusses controversies surrounding our understanding of cardiac energy metabolism in heart failure and the role that PPAR family members may play, either as contributors to or as potential adjunctive therapy for cardiac disease.
Tian
Qi
Q
Barger
Philip M
PM
D000214:Acyl Coenzyme A / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D015536:Down-Regulation / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology*; D006333:Heart Failure / Q000378:metabolism*; D006801:Humans; D008055:Lipids / Q000032:analysis; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism*; D047495:PPAR gamma / Q000502:physiology; D015533:Transcriptional Activation / Q000502:physiology
D000214:Acyl Coenzyme A; D008055:Lipids; D047495:PPAR gamma; D000255:Adenosine Triphosphate