Tontonoz P
Howard Hughes Medical Institute and Department of Pathology and Laboratory Medicine, University of California, Los Angeles, California 90095, USA.
Cold Spring Harb Symp Quant Biol. 2011;76:129-37. doi: 10.1101/sqb.2011.76.010702. Epub 2011 Aug 22.
The liver X receptors (LXRs) are nuclear receptors that play central roles in the transcriptional control of lipid metabolism. LXRs are activated in response to elevated cellular cholesterol levels, allowing them to function as "cholesterol sensors." Once activated, LXRs induce the expression of an array of genes involved in cholesterol absorption, efflux, transport, and excretion. They also inhibit cholesterol uptake by inducing the expression of Idol, an E3 ubiquitin ligase that catalyzes the ubiquitination and degradation of the low-density lipoprotein (LDL) receptor. Synthetic LXR agonists promote cholesterol efflux in vivo and inhibit the development of atherosclerosis in animal models. Conversely, loss of LXR expression in mice leads to pathologic lipid accumulation and accelerated atherosclerosis. The ability of LXRs to coordinate cellular and systemic sterol homeostasis makes them potentially attractive targets for intervention in human metabolic disease.
肝脏X受体（LXRs）是核受体，在脂质代谢的转录控制中起核心作用。LXRs会因细胞胆固醇水平升高而被激活，使其能够作为“胆固醇传感器”发挥作用。一旦被激活，LXRs会诱导一系列参与胆固醇吸收、流出、运输和排泄的基因表达。它们还通过诱导Idol（一种E3泛素连接酶，催化低密度脂蛋白（LDL）受体的泛素化和降解）的表达来抑制胆固醇摄取。合成的LXR激动剂在体内促进胆固醇流出，并在动物模型中抑制动脉粥样硬化的发展。相反，小鼠中LXR表达缺失会导致病理性脂质积累和动脉粥样硬化加速。LXRs协调细胞和全身甾醇稳态的能力使其成为干预人类代谢疾病的潜在有吸引力的靶点。
