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This Article Full Text Full Text (PDF) All Versions of this Article: JOE-09-0271v1 204/3/233    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (1) Google Scholar Articles by Zhao, C. Articles by Dahlman-Wright, K. PubMed PubMed Citation Articles by Zhao, C. Articles by Dahlman-Wright, K.

Department of Biosciences and Nutrition, Novum, Karolinska Institutet, S-141 57 Huddinge, Sweden

(Correspondence should be addressed to K Dahlman-Wright; Email: karin.dahlman-wright{at}ki.se)

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 (NR1H3) and LXRβ (NR1H2). Both LXR and LXRβ regulate gene expression by binding to DNA sequences associated with target genes as heterodimers with isoforms of the retinoid X receptor (RXR), RXR (NR2B1), RXRβ (NR2B2), and RXR (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 and LXRβ isoforms, and the potential use of LXRs as attractive targets for treatment of cardiovascular disease are also discussed.

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