LXR-agonists regulate ApoM expression differentially in liver and intestine

Curr Pharm Biotechnol. 2008 Dec;9(6):516-21. doi: 10.2174/138920108786786376.

Abstract

Apolipoprotein M (apoM) has been suggested to play a role in reverse cholesterol transport. Here we studied the influence of liver X-receptor (LXR) agonist on the transcriptional regulation of apoM. Studies were performed in murine liver and intestinal mucosal cells in vivo and in human intestinal Caco-2 cells in vitro. The expression of apoM was analyzed by quantitative real time PCR, and compared to well-established LXR target genes. Mice fed with TO901317 for six days showed a downregulation of apoM and apoAI in the liver to 40 % and 60 % respectively and an upregulation of Cyp7A1 to 280 %. In the small intestine, however, apoM and apoAI were upregulated by 30-60 % and ABCA1 by 250-430 %. In Caco-2 cells TO901317 caused a 60 % upregulation and the natural LXR agonist 22-hydroxycholesterol a 40 % upregulation of apoM. Possible causes for the differential effects in liver and intestine are discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apolipoproteins / metabolism*
  • Apolipoproteins M
  • Caco-2 Cells
  • DNA-Binding Proteins / drug effects*
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology
  • Humans
  • Hydrocarbons, Fluorinated / administration & dosage*
  • Intestinal Mucosa / metabolism*
  • Intestines / drug effects
  • Lipocalins
  • Liver / drug effects
  • Liver / metabolism*
  • Liver X Receptors
  • Organ Specificity / drug effects
  • Organ Specificity / physiology
  • Orphan Nuclear Receptors
  • Receptors, Cytoplasmic and Nuclear / drug effects*
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • Sulfonamides / administration & dosage*

Substances

  • APOM protein, human
  • Apolipoproteins
  • Apolipoproteins M
  • DNA-Binding Proteins
  • Hydrocarbons, Fluorinated
  • Lipocalins
  • Liver X Receptors
  • Orphan Nuclear Receptors
  • Receptors, Cytoplasmic and Nuclear
  • Sulfonamides
  • T0901317