Bile acid represses the peroxisome proliferator-activated receptor-gamma coactivator-1 promoter activity in a small heterodimer partner-dependent manner.
Int J Mol Med
; 19(5): 751-6, 2007 May.
Article
em En
| MEDLINE
| ID: mdl-17390079
ABSTRACT
Bile acid homeostasis is tightly controlled by the feedback mechanism in which an atypical orphan nuclear receptor (NR), small heterodimer partner (SHP), inactivates several transcription factors. We previously demonstrated that bile acid represses the expression of gluconeogenic genes, including glucose-6-phosphatase (G6Pase), phosphoenolpyruvate carboxykinase (PEPCK), and fructose-1,6-bisphosphatase (FBP1) in an SHP-dependent manner. Recently, peroxisome proliferator-activated receptor-gamma (PPAR-gamma) coactivator-1 (PGC-1) gene, a coactivator of NRs important for gluconeogenic gene expression, was also downregulated by bile acid in wild-type mice but not in farnesoid X receptor- or SHP-null mice. However, the molecular mechanism for the effect of bile acid on PGC-1 gene expression remains unknown. In the present study, a series of reporter assays demonstrated that the promoter activity of PGC-1 via a member of the forkhead transcription factors, Foxo1, FOXO3a, and Foxo4 was downregulated by treatment with chenodeoxicholic acid and with transfected SHP. These results revealed that bile acid inhibits the promoter activity of PGC-1 in an SHP-dependent manner.
Buscar no Google
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Ácidos e Sais Biliares
/
Regulação para Baixo
/
Regiões Promotoras Genéticas
/
Receptores Citoplasmáticos e Nucleares
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article