Regulation of absorption and ABC1-mediated efflux of cholesterol by RXR heterodimers
Regulation of absorption and ABC1-mediated efflux of cholesterol by RXR heterodimers
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DOI：
10.1126/science.289.5484.1524
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发表时间：
2000-09-01
期刊：
影响因子：
56.9
通讯作者：
Mangelsdorf, DJ
中科院分区：
文献类型：
--
作者：
Repa, JJ;Turley, SD;Mangelsdorf, DJ
参与脂质代谢的几种核激素受体与类维生素A X受体（RXR）形成专性异二聚体，并被RXR激动剂（如rexinoids）激活。用类Rexinoids处理的动物表现出胆固醇平衡的显著变化，包括抑制胆固醇吸收和抑制胆汁酸合成。受体选择性激动剂的研究表明，氧固醇受体（LXR）和胆汁酸受体（FXR）是RXR异二聚体伴侣，分别通过调节胆固醇反向转运蛋白ABC 1和胆汁酸合成限速酶CYP 7A1的表达来介导这些效应。因此，这些RXR异二聚体通过控制外周组织的胆固醇反向转运、肝脏中的胆汁酸合成和肠道中的胆固醇吸收，充当胆固醇稳态的关键调节剂。
Several nuclear hormone receptors involved in lipid metabolism form obligate heterodimers with retinoid X receptors (RXRs) and are activated by RXR agonists such as rexinoids. Animals treated with rexinoids exhibited marked changes in cholesterol balance, including inhibition of cholesterol absorption and repressed bile acid synthesis. Studies with receptor-selective agonists revealed that oxysterol receptors (LXRs) and the bile acid receptor (FXR) are the RXR heterodimeric partners that mediate these effects by regulating expression of the reverse cholesterol transporter, ABC1, and the rate-limiting enzyme of bile acid synthesis, CYP7A1, respectively. Thus, these RXR heterodimers serve as key regulators of cholesterol homeostasis by governing reverse cholesterol transport from peripheral tissues, bile acid synthesis in Liver, and cholesterol absorption in intestine.