Liver X receptors: new players in atherogenesis?

The liver X receptors (alpha and beta) are oxysterol-activated nuclear receptors. A large number of liver X receptor target genes with functions in lipid homeostasis have been identified. Increasing evidence indicates that these receptors play a beneficial role in avoiding cholesterol overload by intervening at several steps of cholesterol metabolism. In this review, we describe the most recent developments concerning their functions in cholesterol and lipid metabolism and their impact in atherogenesis. Although potentially undesirable effects of liver X receptor activation on triglyceride metabolism have been observed, recent in-vivo studies confirm that the overall trend is a reduction of atherogenesis. Consequently, liver X receptors are becoming therapeutic targets of great interest for the treatment of atherosclerosis, especially if their action on triglyceride and cholesterol metabolism can be dissociated and isoform-specific ligands identified.