The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
Peroxisome Proliferator-Activated Receptor (PPAR) α and PPARβ/δ, but not PPARγ, Modulate the Expression of Genes Involved in Cardiac Lipid Metabolism
Abstract
Long-chain fatty acids (FA) coordinately induce the expression of a panel of genes involved in cellular FA metabolism in cardiac muscle cells, thereby promoting their own metabolism. These effects are likely to be mediated by peroxisome proliferator-activated receptors (PPARs). Whereas the significance of PPARα in FA-mediated expression has been demonstrated, the role of the PPARβ/δ and PPARγ isoforms in cardiac lipid metabolism is unknown. To explore the involvement of each of the PPAR isoforms, neonatal rat cardiomyocytes were exposed to FA or to ligands specific for either PPARα (Wy-14,643), PPARβ/δ (L-165041, GW501516), or PPARγ (ciglitazone and rosiglitazone). Their effect on FA oxidation rate, expression of metabolic genes, and muscle-type carnitine palmitoyltransferase-1 (MCPT-1) promoter activity was determined. Consistent with the PPAR isoform expression pattern, the FA oxidation rate increased in cardiomyocytes exposed to PPARα and PPARβ/δ ligands, but not to PPARγ ligands. Likewise, the FA-mediated expression of FA-handling proteins was mimicked by PPARα and PPARβ/δ, but not by PPARγ ligands. As expected, in embryonic rat heart-derived H9c2 cells, which only express PPARβ/δ, the FA-induced expression of genes was mimicked by the PPARβ/δ ligand only, indicating that FA also act as ligands for the PPARβ/δ isoform. In cardiomyocytes, MCPT-1 promoter activity was unresponsive to PPARγ ligands. However, addition of PPARα and PPARβ/δ ligands dose-dependently induced promoter activity. Collectively, the present findings demonstrate that, next to PPARα, PPARβ/δ, but not PPARγ, plays a prominent role in the regulation of cardiac lipid metabolism, thereby warranting further research into the role of PPARβ/δ in cardiac disease.
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Cites
Braissant, O., Foufelle, F., Scotto, C., Dauça, M., & Wahli, W. (1996) · Endocrinology · doi:10.1210/endo.137.1.8536636 · Cited by 2,217
The PPARs: From Orphan Receptors to Drug Discovery
Willson, T. M., Brown, P. J., Sternbach, D. D., & Henke, B. R. (2000) · Journal of Medicinal Chemistry · doi:10.1021/jm990554g · Cited by 1,816
de Vries, J. E., Vork, M. M., Roemen, T. H., de Jong, Y. F., Cleutjens, J. P., van der Vusse, G. J., & van Bilsen, M. (1997) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)37421-6 · Cited by 324
Cited by
Sorting out the roles of PPAR in energy metabolism and vascular homeostasis
Lefebvre, P. (2006) · Journal of Clinical Investigation · doi:10.1172/jci27989 · Cited by 962
Transcriptional control of mitochondrial biogenesis: the central role of PGC-1
Ventura-Clapier, R., Garnier, A., & Veksler, V. (2008) · Cardiovascular Research · doi:10.1093/cvr/cvn098 · Cited by 932
Carnitine palmitoyltransferases 1 and 2: biochemical, molecular and medical aspects
BONNEFONT, J. (2004) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2004.06.004 · Cited by 637
Lopaschuk, G. D., & Jaswal, J. S. (2010) · Journal of Cardiovascular Pharmacology · doi:10.1097/fjc.0b013e3181e74a14 · Cited by 636
Marx, N., Duez, H., Fruchart, J.-C., & Staels, B. (2004) · Circulation Research · doi:10.1161/01.res.0000127122.22685.0a · Cited by 501
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Metadata
- Authors
- Gilde, A. J., van der Lee, K. A. J. M., Willemsen, P. H. M., Chinetti, G., van der Leij, F. R., van der Vusse, G. J., Staels, B., & van Bilsen, M.
- Venue
- Circulation Research
- Published
- 2003-03-21
- Volume
- 92
- Issue
- 5
- Pages
- 518-524
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- OpenAlex
- W2097192370
- Cited by
- 399
- References
- 3
- FWCI
- 9.01
- Type
- journal article
- Language
- en
- Open access
- closed
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