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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

Penno, Carlos A. and Morgan, Stuart A. and Rose, Adam J. and Herzig, Stephan and Lavery, Gareth G. and Odermatt, Alex. (2014) 11β-Hydroxysteroid dehydrogenase-1 is involved in bile acid homeostasis by modulating fatty acid transport protein-5 in the liver of mice. Molecular metabolism, Vol. 3, H. 5. pp. 554-564.

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Official URL: http://edoc.unibas.ch/dok/A6298871

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Abstract

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.
Faculties and Departments:05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Molecular and Systems Toxicology (Odermatt)
UniBasel Contributors:Odermatt, Alex
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Elsevier
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:06 Feb 2015 09:58
Deposited On:06 Feb 2015 09:58

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