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11β-Hydroxysteroid dehydrogenase-1 is involved in bile acid homeostasis by modulating fatty acid transport protein-5 in the liver of mice

11β-Hydroxysteroid dehydrogenase-1 (11β-HSD1) plays a key role in glucocorticoid receptor (GR) activation. Besides, it metabolizes some oxysterols and bile acids (BAs). The GR regulates BA homeostasis; however, the impact of impaired 11β-HSD1 activity remained unknown. We profiled plasma and liver B...

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Main Authors: Penno, Carlos A. (Author) , Morgan, Stuart A. (Author) , Rose, Adam J. (Author) , Herzig, Stephan (Author) , Lavery, Gareth G. (Author) , Odermatt, Alex (Author)
Format: Article (Journal)
Language:English
Published: 2 May 2014
In: Molecular metabolism
Year: 2014, Volume: 3, Issue: 5, Pages: 554-564
ISSN:2212-8778
DOI:10.1016/j.molmet.2014.04.008
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.molmet.2014.04.008
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S2212877814000866
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Author Notes:Carlos A. Penno, Stuart A. Morgan, Adam J. Rose, Stephan Herzig, Gareth G. Lavery, Alex Odermatt
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Summary:11β-Hydroxysteroid dehydrogenase-1 (11β-HSD1) plays a key role in glucocorticoid receptor (GR) activation. Besides, it metabolizes some oxysterols and bile acids (BAs). The GR regulates BA homeostasis; however, the impact of impaired 11β-HSD1 activity remained unknown. We profiled plasma and liver BAs in liver-specific and global 11β-HSD1-deficient mice. 11β-HSD1-deficiency resulted in elevated circulating unconjugated BAs, an effect more pronounced in global than liver-specific knockout mice. Gene expression analyses revealed decreased expression of the BA-CoA ligase Fatp5, suggesting impaired BA amidation. Reduced organic anion-transporting polypeptide-1A1 (Oatp1a1) and enhanced organic solute-transporter-β (Ostb) mRNA expression were observed in livers from global 11β-HSD1-deficient mice. The impact of 11β-HSD1-deficiency on BA homeostasis seems to be GR-independent because intrahepatic corticosterone and GR target gene expression were not substantially decreased in livers from global knockout mice. Moreover, Fatp5 expression in livers from hepatocyte-specific GR knockout mice was unchanged. The results revealed a role for 11β-HSD1 in BA homeostasis.
Item Description:Gesehen am 16.02.2021
Physical Description:Online Resource
ISSN:2212-8778
DOI:10.1016/j.molmet.2014.04.008

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