Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2010 Oct 30;62(13):1316-21.
doi: 10.1016/j.addr.2010.07.006. Epub 2010 Jul 24.

Functional crosstalk of CAR-LXR and ROR-LXR in drug metabolism and lipid metabolism

Affiliations
Review

Functional crosstalk of CAR-LXR and ROR-LXR in drug metabolism and lipid metabolism

Lei Xiao et al. Adv Drug Deliv Rev. .

Abstract

Nuclear receptor crosstalk represents an important mechanism to expand the functions of individual receptors. The liver X receptors (LXR, NR1H2/3), both the α and β isoforms, are nuclear receptors that can be activated by the endogenous oxysterols and other synthetic agonists. LXRs function as cholesterol sensors, which protect mammals from cholesterol overload. LXRs have been shown to regulate the expression of a battery of metabolic genes, especially those involved in lipid metabolism. LXRs have recently been suggested to play a novel role in the regulation of drug metabolism. The constitutive androstane receptor (CAR, NR1I3) is a xenobiotic receptor that regulates the expression of drug-metabolizing enzymes and transporters. Disruption of CAR alters sensitivity to toxins, increasing or decreasing it depending on the compounds. More recently, additional roles for CAR have been discovered. These include the involvement of CAR in lipid metabolism. Mechanistically, CAR forms an intricate regulatory network with other members of the nuclear receptor superfamily, foremost the LXRs, in exerting its effect on lipid metabolism. Retinoid-related orphan receptors (RORs, NR1F1/2/3) have three isoforms, α, β and γ. Recent reports have shown that loss of RORα and/or RORγ can positively or negatively influence the expression of multiple drug-metabolizing enzymes and transporters in the liver. The effects of RORs on expression of drug-metabolizing enzymes were reasoned to be, at least in part, due to the crosstalk with LXR. This review focuses on the CAR-LXR and ROR-LXR crosstalk, and the implications of this crosstalk in drug metabolism and lipid metabolism.

PubMed Disclaimer

Similar articles

Cited by

Publication types

MeSH terms

Substances

LinkOut - more resources