Endogenous bile acids are ligands for the nuclear receptor FXR/BAR

Haibo Wang, Jasmine Chen, Kevin Hollister, Lawrence Sowers, Barry M. Forman

Research output: Contribution to journalArticle

1020 Citations (Scopus)

Abstract

The major metabolic pathway for elimination of cholesterol is via conversion to bile acids. In addition to this metabolic function, bile acids also act as signaling molecules that negatively regulate their own biosynthesis. However, the precise nature of this signaling pathway has been elusive. We have isolated an endogenous biliary component (chenodeoxycholic acid) that selectively activates the orphan nuclear receptor, FXR. Structure- activity analysis defined a subset of related bile acid ligands that activate FXR and promote coactivator recruitment. Finally, we show that ligand- occupied FXR inhibits transactivation from the oxysterol receptor LXRα, a positive regulator of cholesterol degradation. We suggest that FXR (BAR) is the endogenous bile acid sensor and thus an important regulator of cholesterol homeostasis.

Original languageEnglish (US)
Pages (from-to)543-553
Number of pages11
JournalMolecular Cell
Volume3
Issue number5
DOIs
StatePublished - 1999
Externally publishedYes

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Cytoplasmic and Nuclear Receptors
Bile Acids and Salts
Ligands
Cholesterol
Orphan Nuclear Receptors
Chenodeoxycholic Acid
Metabolic Networks and Pathways
Transcriptional Activation
Homeostasis

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Endogenous bile acids are ligands for the nuclear receptor FXR/BAR. / Wang, Haibo; Chen, Jasmine; Hollister, Kevin; Sowers, Lawrence; Forman, Barry M.

In: Molecular Cell, Vol. 3, No. 5, 1999, p. 543-553.

Research output: Contribution to journalArticle

Wang, Haibo ; Chen, Jasmine ; Hollister, Kevin ; Sowers, Lawrence ; Forman, Barry M. / Endogenous bile acids are ligands for the nuclear receptor FXR/BAR. In: Molecular Cell. 1999 ; Vol. 3, No. 5. pp. 543-553.
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