Liver X receptors in lipid metabolism: opportunities for drug discovery

Abstract

The liver X receptors (LXRs) are pivotal regulators of lipid homeostasis in mammals. These transcription factors control the expression of a battery of genes involved in the uptake, transport, efflux and excretion of cholesterol in a tissue-dependent manner. The identification of the LXRs, and an increased understanding of the mechanisms by which LXR signalling regulates lipid homeostasis in different tissues (including the liver, intestine and brain), has highlighted new opportunities for therapeutic intervention in human metabolism. New strategies for the pharmacological manipulation of LXRs and their target genes offer promise for the treatment of human diseases in which lipids have a central role, including atherosclerosis and Alzheimer's disease.