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The Farnesoid X-activated Receptor Mediates Bile Acid Activation of Phospholipid Transfer Protein Gene Expression*

Authors :
Urizar, Nancy L.
Dowhan, Dennis H.
Moore, David D.
Source :
Journal of Biological Chemistry; December 2000, Vol. 275 Issue: 50 p39313-39317, 5p
Publication Year :
2000

Abstract

Bile acids facilitate the absorption of dietary lipids and fat-soluble vitamins and are physiological ligands for the farnesoid X-activated receptor (FXR), a member of the nuclear hormone receptor superfamily. FXR functions as 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 promoter contains a potential FXR response element, an inverted repeat in which consensus receptor-binding hexamers are separated by one nucleotide (inverted repeat-1). PLTP is essential in the transfer of very low density lipoprotein 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. Clin. Invest.103, 907–914). Here we report the regulation of PLTP gene expression by FXR and bile acids. In CV-1 cells, cotransfection of FXR and the retinoid X receptor resulted in bile acid-dependent transactivation of a luciferase reporter construct containing the human PLTP promoter. Mutation analysis demonstrated that the inverted repeat-1 (IR-1) 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 supplemented with bile acid showed increased hepatic PLTP mRNA levels. These results suggest that FXR may play a role in high density lipoprotein metabolism via the regulation of PLTP gene expression.

Details

Language :
English
ISSN :
00219258 and 1083351X
Volume :
275
Issue :
50
Database :
Supplemental Index
Journal :
Journal of Biological Chemistry
Publication Type :
Periodical
Accession number :
ejs7152758
Full Text :
https://doi.org/10.1074/jbc.M007998200