title: Cholestenoic acid is a naturally occurring ligand for liver X receptor alpha.
abstract: 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 3beta-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.
authors.affiliation: Ben May Institute for Cancer Research, University of Chicago, Illinois 60637, USA.
authors.forename: C
authors.initials: C
authors.lastname: Song
authors.forename: S
authors.initials: S
authors.lastname: Liao
mesh_terms: D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D004268:DNA-Binding Proteins; D004622:Embryo, Mammalian; D017930:Genes, Reporter; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D007668:Kidney; D008024:Ligands; D050356:Lipid Metabolism; D000071518:Liver X Receptors; D008156:Luciferases / Q000235:genetics; D051958:Nuclear Receptor Coactivator 2; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D011988:Receptors, Thyroid Hormone / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: D004268:DNA-Binding Proteins; D008024:Ligands; D000071518:Liver X Receptors; C498001:NCOA2 protein, human; C000605213:NR1H3 protein, human; D051958:Nuclear Receptor Coactivator 2; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; C029435:3-hydroxy-5-cholestenoic acid; D002784:Cholesterol; D008156:Luciferases; D005982:Glutathione Transferase