Lipid-activated transcription factors control bile acid glucuronidation

  • Olivier Barbier
  • Jocelyn Trottier
  • Jenny Kaeding
  • Patrick Caron
  • Mélanie Verreault
Article

DOI: 10.1007/s11010-008-0001-5

Cite this article as:
Barbier, O., Trottier, J., Kaeding, J. et al. Mol Cell Biochem (2009) 326: 3. doi:10.1007/s11010-008-0001-5

Abstract

Bile acids subserve important physiological functions in the control of cholesterol homeostasis. Indeed, hepatic bile acid synthesis and biliary excretion constitute the main route for cholesterol removal from the human body. On the other hand, bile acids serve as natural detergents for the intestinal absorption of dietary cholesterol. However, due to their detergent properties, bile acids are inherently cytotoxic, and their cellular level may be tightly controlled to avoid pathological situations such as cholestasis. Recent investigations have illustrated the crucial roles that a series of ligand-activated transcription factors has in the control of hepatic bile acids synthesis, transport and metabolism. Thus, the lipid-activated nuclear receptors, farnesoid X-receptor (FXR), liver X-receptor (LXR), pregnane X-receptor (PXR) and peroxisome proliferator-activated receptor alpha (PPARα), modulate the expression and activity of genes controlling bile acid homeostasis in the liver. Several members of the UDP-glucuronosyltransferase (UGT) enzymes family are among the bile acid metabolizing enzymes regulated by these receptors. UGTs catalyze glucuronidation, a major phase II metabolic reaction, which converts hydrophobic bile acids into polar and urinary excretable metabolites. This article summarizes our recent observations on the regulation of bile acid conjugating UGTs upon pharmacological activation of lipid-activated receptors, with a particular interest for the role of PPARα and LXRα in controlling human UGT1A3 expression.

Keywords

Bile acidGlucuronidationPPARαLXRαUGT1A3

Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • Olivier Barbier
    • 1
    • 2
    • 3
  • Jocelyn Trottier
    • 1
    • 2
  • Jenny Kaeding
    • 1
    • 2
  • Patrick Caron
    • 1
    • 2
  • Mélanie Verreault
    • 1
    • 2
  1. 1.Laboratory of Molecular Pharmacology, Endocrinology and GenomicCHUL Research Center, Laval UniversityQuébecCanada
  2. 2.Faculty of PharmacyLaval UniversityQuébecCanada
  3. 3.Laboratory of Molecular PharmacologyCHUQ-CHUL Research CenterQuebecCanada