Zhang Yuan, Mangelsdorf David J
Department of Pharmacology, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, Tx 75390-9050, USA.
Mol Interv. 2002 Apr;2(2):78-87. doi: 10.1124/mi.2.2.78.
Cholesterol homeostasis is maintained by a regulatory network that controls both the acquisition and elimination of cholesterol. Recent studies have elucidated a mechanism by which cholesterol metabolism is transcriptionally regulated by several classes of orphan nuclear receptors. In particular, the liver X receptors, LXRalpha and LXRbeta, appear to serve as key sensors of intracellular sterol levels by regulating the expression of genes that control cholesterol absorption, storage, transport, and elimination. LXRs are also involved in fatty acid metabolism by their ability to increase the expression of sterol regulatory element-binding protein 1c (SREBP-1c). These findings define LXRs as potential therapeutic targets for the treatment of lipid disorders.
胆固醇稳态由一个控制胆固醇获取和清除的调节网络维持。最近的研究阐明了一种机制,通过该机制胆固醇代谢受到几类孤儿核受体的转录调控。特别是,肝脏X受体LXRα和LXRβ,似乎通过调节控制胆固醇吸收、储存、运输和清除的基因表达,充当细胞内固醇水平的关键传感器。LXRs还通过增加固醇调节元件结合蛋白1c(SREBP-1c)的表达参与脂肪酸代谢。这些发现将LXRs定义为治疗脂质紊乱的潜在治疗靶点。