Differential regulation of the expressions of the PGC-1α splice variants, lipins, and PPARα in heart compared to liver
Autor: | David N. Brindley, Thurl E. Harris, Jason R.B. Dyck, Bernard P. Kok |
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Rok vydání: | 2013 |
Předmět: |
medicine.medical_specialty
QD415-436 Biology Biochemistry Rats Sprague-Dawley Endocrinology Downregulation and upregulation Internal medicine Coactivator medicine Animals Myocytes Cardiac PPAR alpha Carnitine glycerolipid Organic Chemicals Receptor Gene Research Articles Messenger RNA hepatic and cardiac gene regulation Myocardium Fatty Acids phosphatidate phosphatase Fasting Cell Biology Peroxisome Phosphatidate phosphatase Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha Rats Alternative Splicing Gene Expression Regulation Liver Organ Specificity Oxidation-Reduction Transcription Factors medicine.drug |
Zdroj: | Journal of Lipid Research, Vol 54, Iss 6, Pp 1662-1677 (2013) |
ISSN: | 0022-2275 |
Popis: | 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. |
Databáze: | OpenAIRE |
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