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Biochim Biophys Acta. 2003 Mar 17;1631(2):107-18.

Liver X receptors and the control of cholesterol homeostasis: potential therapeutic targets for the treatment of atherosclerosis.

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  • 1Facult√© de Pharmacie, Universit√© de Lille II, Lille, France.


The liver X receptors (LXRalpha and LXRbeta) are nuclear receptor transcription factors that are activated by certain oxysterol derivatives of cholesterol. As such, LXR activity may be up-regulated by cellular lipid loading or dietary cholesterol intake. Intensive research interest in the LXRs has led to the identification of an expanding list of LXR target genes. The identity of these genes, and their response to LXR activation, indicates that the LXRs play an important role in the response to excess cholesterol, and that their activation may protect against tissue cholesterol overload. In this review, we highlight the multiple roles of the LXRs in controlling cholesterol homeostasis via their coordinated effects on cholesterol synthesis, dietary cholesterol absorption, reverse cholesterol transport, and bile acid synthesis and excretion. We discuss the therapeutic interest of developing LXR agonists, in view of their apparent protective effects against atherosclerosis. However, we also draw attention to the possible undesirable side-effects of LXR activation, and thus the potential interest of developing target gene-specific LXR agonists, or agonists that are specific for only one LXR isoform.

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