Identification of a nuclear receptor for bile acids

Science. 1999 May 21;284(5418):1362-5. doi: 10.1126/science.284.5418.1362.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bile Acids and Salts / biosynthesis
  • Bile Acids and Salts / metabolism*
  • Biological Transport
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism
  • Cell Line
  • Chenodeoxycholic Acid / metabolism*
  • Cholesterol / metabolism
  • Cholesterol 7-alpha-Hydroxylase / genetics*
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation
  • Histone Acetyltransferases
  • Homeostasis
  • Humans
  • Hydroxysteroid Dehydrogenases*
  • Ligands
  • Liver / metabolism
  • Membrane Glycoproteins*
  • Mice
  • Nuclear Receptor Coactivator 1
  • Organic Anion Transporters, Sodium-Dependent*
  • Receptors, Cytoplasmic and Nuclear / chemistry
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Symporters*
  • Transcription Factors / chemistry
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transfection
  • Tumor Cells, Cultured

Substances

  • Bile Acids and Salts
  • Carrier Proteins
  • DNA-Binding Proteins
  • Ligands
  • Membrane Glycoproteins
  • Organic Anion Transporters, Sodium-Dependent
  • Receptors, Cytoplasmic and Nuclear
  • Symporters
  • Transcription Factors
  • bile acid binding proteins
  • farnesoid X-activated receptor
  • Chenodeoxycholic Acid
  • sodium-bile acid cotransporter
  • Cholesterol
  • Hydroxysteroid Dehydrogenases
  • AKR1C2 protein, human
  • Cholesterol 7-alpha-Hydroxylase
  • Histone Acetyltransferases
  • NCOA1 protein, human
  • Ncoa1 protein, mouse
  • Nuclear Receptor Coactivator 1