The farnesoid X-activated receptor mediates bile acid activation of phospholipid transfer protein gene expression

Citation
Nl. Urizar et al., The farnesoid X-activated receptor mediates bile acid activation of phospholipid transfer protein gene expression, J BIOL CHEM, 275(50), 2000, pp. 39313-39317
Citations number
28
Categorie Soggetti
Biochemistry & Biophysics
Journal title
JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN journal
00219258 → ACNP
Volume
275
Issue
50
Year of publication
2000
Pages
39313 - 39317
Database
ISI
SICI code
0021-9258(200012)275:50<39313:TFXRMB>2.0.ZU;2-5
Abstract
Bile acids facilitate the absorption of dietary lipids and fat-soluble vita mins and are physiological ligands for the farnesoid X-activated receptor ( FXR), a member of the nuclear hormone receptor superfamily, FXR functions a s a heterodimer with the retinoid X receptor and in the presence of ligand, the heterodimer binds to specific DNA sequences in the promoters of target genes to regulate gene transcription. Phospholipid transfer protein (PLTP) has been identified as a possible target gene for FXR because the human pr omoter contains a potential FXR response element, an inverted repeat in whi ch consensus receptor-binding hexamers are separated by one nucleotide (inv erted repeat-1). PLTP is essential in the transfer of very low density lipo protein phospholipids into high density lipoprotein (Jiang, X, C., Bruce, C ., Mar, J., Lin, M., Ji, Y., Francone, O. L., and Tall, A. R. (1999) J. Cli n. Invest. 103, 907-914), Here we report the regulation of PLTP gene expres sion by FXR and bile acids. In CV-1 cells, cotransfection of FXR and the re tinoid X receptor resulted in bile acid-dependent transactivation of a luci ferase reporter construct containing the human PLTP promoter. Mutation anal ysis demonstrated that the inverted repeat-1 (IR-l) in the PLTP promoter is required for this transactivation. Finally, we demonstrate that bile acids are able to regulate PLTP gene expression in vivo. Mice fed a chow diet su pplemented with bile acid showed increased hepatic PLTP mRNA levels. These results suggest that FXR may play a role in high density lipoprotein metabo lism via the regulation of PLTP gene expression.