Inhibition of peroxisome proliferator-activated receptor alpha signaling by vitamin D receptor.
Biochem Biophys Res Commun
; 312(2): 513-9, 2003 Dec 12.
Article
em En
| MEDLINE
| ID: mdl-14637167
ABSTRACT
Peroxisome proliferator-activated receptors (PPARs) are nuclear fatty acid receptors that have been implicated to play an important role in lipid and glucose homeostasis. PPARalpha potentiates fatty acid catabolism in the liver and is activated by the lipid-lowering fibrates, whereas PPARgamma is essential for adipocyte differentiation. Here we report that nuclear vitamin D(3) receptor (VDR) represses the transcriptional activity of PPARalpha but not PPARgamma in a 1,25(OH)(2)D(3)-dependent manner. The analysis using chimeric receptors revealed that ligand binding domain of PPARalpha and VDR was involved in the molecular basis of this functional interaction and that the DNA binding domain of VDR was not required for the suppression, suggesting a novel mechanism that might involve protein-protein interactions rather than a direct DNA binding. Furthermore, the treatment of rat hepatoma H4IIE cells with 1,25(OH)(2)D(3) diminishes the induction of AOX mRNA by PPARalpha ligands, Wy14,643. VDR signaling might be considered as a factor regulating lipid metabolism via PPARalpha pathway. We report here the novel action of VDR in controlling gene expression through PPARalpha signaling.
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Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Calcitriol
/
Transdução de Sinais
/
Regulação da Expressão Gênica
/
Receptores Citoplasmáticos e Nucleares
/
Receptores de Calcitriol
Limite:
Animals
Idioma:
En
Ano de publicação:
2003
Tipo de documento:
Article