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Journal of Lipid Research, Vol. 45, 2161-2173, December 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology
Thematic Review |
PPAR- and LXR-dependent pathways controlling lipid metabolism and the development of atherosclerosis
Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093
1 To whom correspondence should be addressed. e-mail: cglass{at}ucsd.edu
The nuclear receptor superfamily is composed of transcription factors that positively and negatively regulate gene expression in response to the binding of a diverse array of lipid-derived hormones and metabolites. Intense efforts are currently being directed at defining the biological roles and mechanisms of action of liver X receptors (LXRs) and peroxisome proliferator-activated receptors (PPARs). LXRs have been found to play essential roles in the regulation of whole body cholesterol absorption and excretion, in the efflux of cholesterol from peripheral cells, and in the biosynthesis and metabolism of very low density lipoproteins. PPARs have been found to regulate diverse aspects of lipid metabolism, including fatty acid oxidation, fat cell development, lipoprotein metabolism, and glucose homeostasis. Intervention studies indicate that activation of PPAR
, PPAR
, and LXRs by specific synthetic ligands can inhibit the development of atherosclerosis in animal models.
Here, we review recent studies that provide new insights into the mechanisms by which these subclasses of nuclear receptors act to systemically influence lipid and glucose metabolism and regulate gene expression within the artery wall.
Supplementary key words peroxisome proliferator-activated receptors • liver X receptors • foam cell formation
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