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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Cell Line
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Cell Nucleus / metabolism
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Cholesterol / analogs & derivatives*
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Cholesterol / metabolism*
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Cholesterol / pharmacology
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DNA-Binding Proteins
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Embryo, Mammalian
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Genes, Reporter
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Glutathione Transferase / genetics
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Humans
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Kidney
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Ligands
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Lipid Metabolism
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Liver X Receptors
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Luciferases / genetics
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Nuclear Receptor Coactivator 2
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Orphan Nuclear Receptors
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Receptors, Cytoplasmic and Nuclear*
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Receptors, Retinoic Acid / drug effects
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Receptors, Retinoic Acid / genetics
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Receptors, Retinoic Acid / metabolism*
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Receptors, Thyroid Hormone / drug effects
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Receptors, Thyroid Hormone / genetics
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Receptors, Thyroid Hormone / metabolism*
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Recombinant Fusion Proteins / metabolism
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Signal Transduction
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Transcription Factors / metabolism
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Transcriptional Activation
Substances
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DNA-Binding Proteins
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Ligands
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Liver X Receptors
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NCOA2 protein, human
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NR1H3 protein, human
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Nuclear Receptor Coactivator 2
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Orphan Nuclear Receptors
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Receptors, Cytoplasmic and Nuclear
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Receptors, Retinoic Acid
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Receptors, Thyroid Hormone
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Recombinant Fusion Proteins
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Transcription Factors
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3-hydroxy-5-cholestenoic acid
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Cholesterol
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Luciferases
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Glutathione Transferase