Bile acids: natural ligands for an orphan nuclear receptor

Science. 1999 May 21;284(5418):1365-8. doi: 10.1126/science.284.5418.1365.

Abstract

Bile acids regulate the transcription of genes that control cholesterol homeostasis through molecular mechanisms that are poorly understood. Physiological concentrations of free and conjugated chenodeoxycholic acid, lithocholic acid, and deoxycholic acid activated the farnesoid X receptor (FXR; NR1H4), an orphan nuclear receptor. As ligands, these bile acids and their conjugates modulated interaction of FXR with a peptide derived from steroid receptor coactivator 1. These results provide evidence for a nuclear bile acid signaling pathway that may regulate cholesterol homeostasis.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bile Acids and Salts / chemistry
  • Bile Acids and Salts / metabolism*
  • Bile Acids and Salts / pharmacology
  • Carrier Proteins / metabolism
  • Cell Line
  • Chenodeoxycholic Acid / metabolism*
  • Chenodeoxycholic Acid / pharmacology
  • Cholesterol / metabolism
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Deoxycholic Acid / metabolism
  • Deoxycholic Acid / pharmacology
  • Histone Acetyltransferases
  • Homeostasis
  • Humans
  • Ligands
  • Lithocholic Acid / metabolism
  • Lithocholic Acid / pharmacology
  • Mice
  • Nuclear Receptor Coactivator 1
  • Organic Anion Transporters, Sodium-Dependent*
  • Protein Conformation
  • Receptors, Cytoplasmic and Nuclear / chemistry
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Recombinant Fusion Proteins / metabolism
  • Signal Transduction
  • Structure-Activity Relationship
  • Symporters*
  • Transcription Factors / chemistry
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transfection

Substances

  • Bile Acids and Salts
  • Carrier Proteins
  • DNA-Binding Proteins
  • Ligands
  • Organic Anion Transporters, Sodium-Dependent
  • Receptors, Cytoplasmic and Nuclear
  • Recombinant Fusion Proteins
  • Symporters
  • Transcription Factors
  • Deoxycholic Acid
  • farnesoid X-activated receptor
  • Chenodeoxycholic Acid
  • sodium-bile acid cotransporter
  • Lithocholic Acid
  • Cholesterol
  • Histone Acetyltransferases
  • NCOA1 protein, human
  • Ncoa1 protein, mouse
  • Nuclear Receptor Coactivator 1