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Endocrinology Vol. 141, No. 11 4180-4184
Copyright © 2000 by The Endocrine Society

ARTICLES

Cholestenoic Acid Is a Naturally Occurring Ligand for Liver X Receptor {alpha}1

Ching Song and Shutsung Liao

Ben May Institute for Cancer Research, University of Chicago, Chicago, Illinois 60637

Address all correspondence and requests for reprints to: Dr. Shutsung Liao, Ben May Institute for Cancer Research, University of Chicago, 5841 South Maryland Avenue, Chicago, Illinois 60637. E-mail: sliao{at}ben-may.bsd.uchicago.edu

Excessive cholesterol is eliminated from extrahepatic cells by reverse cholesterol transport, a process by which neutral sterols are transferred to extracellular acceptor lipoproteins for further transport to the liver. Another process independent of lipoproteins involves excretion of 3ß-hydroxy-5-cholesten-25(R)-26-carboxylic (cholestenoic) acid, a metabolite of 27-hydroxycholesterol. Physiological concentrations of cholestenoic acid activated the nuclear receptor liver X receptor {alpha} (LXR{alpha}; NR1H3), but not other oxysterol receptors. As a ligand, cholestenoic acid modulated interaction of LXR{alpha} with the nuclear receptor coactivator Grip-1. Cholestenoic acid, therefore, may function as a signaling molecule for regulation of lipid metabolism via LXR{alpha}.




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