| First Author | Penno CA | Year | 2014 |
| Journal | Mol Metab | Volume | 3 |
| Issue | 5 | Pages | 554-64 |
| PubMed ID | 25061560 | Mgi Jnum | J:221395 |
| Mgi Id | MGI:5639006 | Doi | 10.1016/j.molmet.2014.04.008 |
| Citation | Penno CA, et al. (2014) 11beta-Hydroxysteroid dehydrogenase-1 is involved in bile acid homeostasis by modulating fatty acid transport protein-5 in the liver of mice. Mol Metab 3(5):554-64 |
| abstractText | 11beta-Hydroxysteroid dehydrogenase-1 (11beta-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 11beta-HSD1 activity remained unknown. We profiled plasma and liver BAs in liver-specific and global 11beta-HSD1-deficient mice. 11beta-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-beta (Ostb) mRNA expression were observed in livers from global 11beta-HSD1-deficient mice. The impact of 11beta-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 11beta-HSD1 in BA homeostasis. |
