Abstract

The liver X receptors α and β are orphan nuclear receptors that are key regulators in maintaining cholesterol homeostasis. Originally they were found to play an important role in reverse cholesterol transport, a pathway for the removal of excess cellular cholesterol. However several groups have now shown that the liver X receptors also functions in lipid and carbohydrate metabolism, cellular differentiation, apoptosis and many immune responses. Tissue distribution of the two paralogues differs with liver X receptor β ubiquitously expressed, while liver X receptor α is confined to the liver, kidney, intestine, spleen, adipose tissue, macrophages and skeletal muscle. The endogenous ligands for the liver X receptors are certain oxidized derivatives of cholesterol, the oxysterols. Upon activation by oxysterols, the receptors form obligate heterodimers with retinoid X receptors α, β and γ; and become competent to activate the transcription of target genes.