RGD Reference Report - Peroxisome proliferator-activated receptor (PPAR) alpha and PPARbeta/delta, but not PPARgamma, modulate the expression of genes involved in cardiac lipid metabolism. - Rat Genome Database

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Peroxisome proliferator-activated receptor (PPAR) alpha and PPARbeta/delta, but not PPARgamma, modulate the expression of genes involved in cardiac lipid metabolism.

Authors: Gilde, AJ  Van der Lee, KA  Willemsen, PH  Chinetti, G  Van der Leij, FR  Van der Vusse, GJ  Staels, B  Van Bilsen, M 
Citation: Gilde AJ, etal., Circ Res 2003 Mar 21;92(5):518-24.
RGD ID: 633661
Pubmed: PMID:12600885   (View Abstract at PubMed)
DOI: DOI:10.1161/01.RES.0000060700.55247.7C   (Journal Full-text)

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 PPARalpha in FA-mediated expression has been demonstrated, the role of the PPARbeta/delta and PPARgamma 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 PPARalpha (Wy-14,643), PPARbeta/delta (L-165041, GW501516), or PPARgamma (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 PPARalpha and PPARbeta/delta ligands, but not to PPARgamma ligands. Likewise, the FA-mediated expression of FA-handling proteins was mimicked by PPARalpha and PPARbeta/delta, but not by PPARgamma ligands. As expected, in embryonic rat heart-derived H9c2 cells, which only express PPARbeta/delta, the FA-induced expression of genes was mimicked by the PPARbeta/delta ligand only, indicating that FA also act as ligands for the PPARbeta/delta isoform. In cardiomyocytes, MCPT-1 promoter activity was unresponsive to PPARgamma ligands. However, addition of PPARalpha and PPARbeta/delta ligands dose-dependently induced promoter activity. Collectively, the present findings demonstrate that, next to PPARalpha, PPARbeta/delta, but not PPARgamma, plays a prominent role in the regulation of cardiac lipid metabolism, thereby warranting further research into the role of PPARbeta/delta in cardiac disease.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
fatty acid metabolic process  IMP 633661 RGD 
fatty acid oxidation  IDA 633661 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
fatty acid binding  IDA 633661 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ppara  (peroxisome proliferator activated receptor alpha)
Ppard  (peroxisome proliferator-activated receptor delta)

Objects referenced in this article
Gene PPARD peroxisome proliferator activated receptor delta Homo sapiens
Gene Ppard peroxisome proliferator activator receptor delta Mus musculus
Gene Ppargc1a PPARG coactivator 1 alpha Rattus norvegicus

Additional Information