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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| Hauptverfasser: | , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
2 May 2014
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| In: |
Molecular metabolism
Year: 2014, Jahrgang: 3, Heft: 5, Pages: 554-564 |
| ISSN: | 2212-8778 |
| DOI: | 10.1016/j.molmet.2014.04.008 |
| Online-Zugang: | 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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| Verfasserangaben: | Carlos A. Penno, Stuart A. Morgan, Adam J. Rose, Stephan Herzig, Gareth G. Lavery, Alex Odermatt |
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| 520 | |a 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. | ||
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| 650 | 4 | |a Bile acid conjugation | |
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