title: Differential regulation of the expressions of the PGC-1α splice variants, lipins, and PPARα in heart compared to liver.
abstract: Peroxisome proliferator-activated receptor α (PPARα) and PPARγ coactivator 1α (PGC-1α) are crucial transcriptional regulators for genes involved in FA oxidation. Lipin-1 is essential for this increased capacity for β-oxidation in fasted livers, and it is also a phosphatidate phosphatase involved in triacylglycerol and phospholipid synthesis. Little is known about the regulation of these proteins in the heart during fasting, where there is increased FA esterification and oxidation. Lipin-1, lipin-2, lipin-3, carnitine palmitoyltransferase-1b (Cpt1b), and PGC-1α-b mRNA were increased by glucocorticoids and cAMP in neonatal rat cardiomyocytes. However, Cpt1b upregulation was caused by increased PPARα activation rather than expression. By contrast, the effects of PPARα in fasted livers are mediated through increased expression. During fasting, the expressions of PGC-1α-b and PGC-1α-c are increased in mouse hearts, and this is explained by increased cAMP-dependent signaling. By contrast, PGC-1α-a expression is increased in liver. Contrary to our expectations, lipin-1 expression was decreased and lipin-2 remained unchanged in hearts compared with increases in fasted livers. Our results identify novel differences in the regulation of lipins, PPARα, and PGC-1α splice variants during fasting in heart versus liver, even though the ultimate outcome in both tissues is to increase FA turnover and oxidation.
authors.affiliation: Signal Transduction Research Group, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Bernard P C
authors.initials: BPC
authors.lastname: Kok
authors.affiliation: Department of Biochemistry, and Cardiovascular Research Centre, University of Alberta, Edmonton, Alberta, Canada; Department of Pediatrics, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Jason R B
authors.initials: JRB
authors.lastname: Dyck
authors.affiliation: Department of Pharmacology, University of Virginia School of Medicine, Charlottesville, Virginia.
authors.forename: Thurl E
authors.initials: TE
authors.lastname: Harris
authors.affiliation: Signal Transduction Research Group, University of Alberta, Edmonton, Alberta, Canada; Department of Pediatrics, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada. Electronic address: david.brindley@ualberta.ca.
authors.forename: David N
authors.initials: DN
authors.lastname: Brindley
mesh_terms: D017398:Alternative Splicing / Q000502:physiology*; D000818:Animals; D005215:Fasting / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D008099:Liver / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D009928:Organ Specificity / Q000502:physiology; D009930:Organic Chemicals / Q000378:metabolism; D010084:Oxidation-Reduction; D047493:PPAR alpha / Q000096:biosynthesis*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D051381:Rats; D017207:Rats, Sprague-Dawley; D014157:Transcription Factors / Q000096:biosynthesis*
chemical_list: D005227:Fatty Acids; D009930:Organic Chemicals; D047493:PPAR alpha; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D014157:Transcription Factors; C088310:lipine
keywords: fasting; glycerolipid; hepatic and cardiac gene regulation; phosphatidate phosphatase