title: Identification of a nuclear receptor for bile acids.
abstract: Bile acids are essential for the solubilization and transport of dietary lipids and are the major products of cholesterol catabolism. Results presented here show that bile acids are physiological ligands for the farnesoid X receptor (FXR), an orphan nuclear receptor. When bound to bile acids, FXR repressed transcription of the gene encoding cholesterol 7alpha-hydroxylase, which is the rate-limiting enzyme in bile acid synthesis, and activated the gene encoding intestinal bile acid-binding protein, which is a candidate bile acid transporter. These results demonstrate a mechanism by which bile acids transcriptionally regulate their biosynthesis and enterohepatic transport.
authors.affiliation: Howard Hughes Medical Institute and Department of Pharmacology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75235-9050, USA.
authors.forename: M
authors.initials: M
authors.lastname: Makishima
authors.forename: A Y
authors.initials: AY
authors.lastname: Okamoto
authors.forename: J J
authors.initials: JJ
authors.lastname: Repa
authors.forename: H
authors.initials: H
authors.lastname: Tu
authors.forename: R M
authors.initials: RM
authors.lastname: Learned
authors.forename: A
authors.initials: A
authors.lastname: Luk
authors.forename: M V
authors.initials: MV
authors.lastname: Hull
authors.forename: K D
authors.initials: KD
authors.lastname: Lustig
authors.forename: D J
authors.initials: DJ
authors.lastname: Mangelsdorf
authors.forename: B
authors.initials: B
authors.lastname: Shan
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000096:biosynthesis / Q000378:metabolism*; D001692:Biological Transport; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D002635:Chenodeoxycholic Acid / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism; D002790:Cholesterol 7-alpha-Hydroxylase / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D051548:Histone Acetyltransferases; D006706:Homeostasis; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases; D008024:Ligands; D008099:Liver / Q000378:metabolism; D008562:Membrane Glycoproteins; D051379:Mice; D056920:Nuclear Receptor Coactivator 1; D029363:Organic Anion Transporters, Sodium-Dependent; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D027981:Symporters; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured; D000099150:Receptor, Farnesoid X-Activated; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific)
chemical_list: D001647:Bile Acids and Salts; D002352:Carrier Proteins; D002635:Chenodeoxycholic Acid; D002784:Cholesterol; D002790:Cholesterol 7-alpha-Hydroxylase; D004268:DNA-Binding Proteins; D051548:Histone Acetyltransferases; D006913:Hydroxysteroid Dehydrogenases; D008024:Ligands; D008562:Membrane Glycoproteins; D056920:Nuclear Receptor Coactivator 1; D029363:Organic Anion Transporters, Sodium-Dependent; D018160:Receptors, Cytoplasmic and Nuclear; D027981:Symporters; D014157:Transcription Factors; D000099150:Receptor, Farnesoid X-Activated; C037643:bile acid binding proteins; C071908:sodium-bile acid cotransporter; C435496:AKR1C2 protein, human; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific); C538859:NCOA1 protein, human; C538861:Ncoa1 protein, mouse