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Modulation of Retinoic Acid Receptor-related Orphan Receptor α and γ Activity by 7-Oxygenated Sterol Ligands
How 7-oxygenated sterols affect the activity of retinoic acid receptor-related orphan receptors alpha and gamma
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Abstract
7-oxygenated sterols are identified as high affinity ligands for both RORalpha and RORgamma, with a binding affinity of approximately 20 nM.
- 7-oxygenated sterols directly bind to the ligand-binding domains of RORalpha and RORgamma, affecting their function.
- These ligands modulate coactivator binding and suppress the transcriptional activity of the receptors.
- One specific sterol, 7alpha-hydroxycholesterol (7alpha-OHC), is a significant intermediate in bile acid metabolism.
- 7alpha-OHC influences the expression of ROR target genes, such as Glc-6-Pase and phosphoenolpyruvate carboxykinase, in a manner dependent on ROR.
- The presence of 7alpha-OHC reduces glucose output from liver cells by acting as a ligand for RORalpha and RORgamma.
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