The PPAR trio: regulators of myocardial energy metabolism in health and disease.
Common causes of heart failure are associated with derangements in myocardial fuel utilization. Evidence is emerging that metabolic abnormalities may contribute to the development and progression of myocardial disease. The peroxisome proliferator-activated receptor (PPAR) family of nuclear receptor transcription factors has been shown to regulate cardiac fuel metabolism at the gene expression level. The three PPAR family members (alpha, beta/delta and gamma) are uniquely suited to serve as transducers of developmental, physiological, and dietary cues that influence cardiac fatty acid and glucose metabolism. This review describes murine PPAR loss- and gain-of-function models that have shed light on the roles of these receptors in regulating myocardial metabolic pathways and have defined key links to disease states including the hypertensive and diabetic heart.
Madrazo
Jose A
JA
Center for Cardiovascular Research, Washington University School of Medicine, St. Louis, Missouri, USA; Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
Kelly
Daniel P
DP
Center for Cardiovascular Research, Washington University School of Medicine, St. Louis, Missouri, USA; Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA; Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, Missouri, USA; Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA. Electronic address: dkelly@im.wustl.edu.
D000818:Animals; D003920:Diabetes Mellitus / Q000235:genetics / Q000378:metabolism; D004734:Energy Metabolism / Q000235:genetics; D005227:Fatty Acids / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics; D005947:Glucose / Q000235:genetics / Q000378:metabolism*; D006333:Heart Failure / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006973:Hypertension / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009206:Myocardium / Q000378:metabolism*; D047492:Peroxisome Proliferator-Activated Receptors / Q000235:genetics / Q000378:metabolism*
D005227:Fatty Acids; D047492:Peroxisome Proliferator-Activated Receptors; D005947:Glucose