Liver X receptor in cholesterol metabolism

J Endocrinol. 2010 Mar;204(3):233-40. doi: 10.1677/JOE-09-0271. Epub 2009 Oct 16.

Abstract

The liver X receptors (LXRs) are nuclear receptors that are activated by endogenous oxysterols, oxidized derivatives of cholesterol. There are two isoforms of LXR, LXRalpha (NR1H3) and LXRbeta (NR1H2). Both LXRalpha and LXRbeta regulate gene expression by binding to DNA sequences associated with target genes as heterodimers with isoforms of the retinoid X receptor (RXR), RXRalpha (NR2B1), RXRbeta (NR2B2), and RXRgamma (NR2B3). LXRs act as cholesterol sensors: when cellular oxysterols accumulate as a result of increasing concentrations of cholesterol, LXR induces the transcription of genes that protect cells from cholesterol overload. In this review, we summarize the roles of LXRs in controlling cholesterol homeostasis, including their roles in bile acid synthesis and metabolism/excretion, reverse cholesterol transport, cholesterol biosynthesis and uptake, and cholesterol absorption/excretion in the intestine. The overlapping and distinct roles of the LXRalpha and LXRbeta isoforms, and the potential use of LXRs as attractive targets for treatment of cardiovascular disease are also discussed.

Publication types

  • Review

MeSH terms

  • Animals
  • Cholesterol / metabolism*
  • Humans
  • Intestinal Mucosa / metabolism
  • Liver X Receptors
  • Orphan Nuclear Receptors / genetics
  • Orphan Nuclear Receptors / metabolism*
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Retinoid X Receptors / genetics
  • Retinoid X Receptors / metabolism

Substances

  • Liver X Receptors
  • NR1H2 protein, human
  • NR1H3 protein, human
  • Orphan Nuclear Receptors
  • Protein Isoforms
  • Retinoid X Receptors
  • Cholesterol