Liver X receptor in cholesterol metabolism

The liver X receptors (LXRs) are nuclear receptors that are activated by endogenous oxysterols, oxidized derivatives of cholesterol. There are two isoforms of LXR, LXR alpha (NR1H3) and LXR beta (NR1H2). Both LXR alpha and LXR beta regulate gene expression by binding to DNA sequences associated with target genes as heterodimers with isoforms of the retinoid X receptor (RXR), RXR alpha (NR2B1), RXR beta (NR2B2), and RXR gamma (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 LXR alpha and LXR beta isoforms, and the potential use of LXRs as attractive targets for treatment of cardiovascular disease are also discussed. Journal of Endocrinology (2010) 204, 233-240