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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 micea
- Source :
- Molecular Metabolism, Molecular metabolism
- Publication Year :
- 2014
- Publisher :
- Elsevier, 2014.
-
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.
- Subjects :
- medicine.medical_specialty
Bile acid transport
medicine.drug_class
farnesoid X receptor, Fxr
Biology
Cholesterol 7 alpha-hydroxylase
fatty acid transport protein, Fatp
03 medical and health sciences
0302 clinical medicine
Glucocorticoid receptor
Internal medicine
Gene expression
Bile acid conjugation
medicine
BAAT
Molecular Biology
Glucocorticoids
030304 developmental biology
0303 health sciences
Na+-taurocholate cotransporting polypeptide, Ntcp
Bile acid
cholesterol 7α-hydroxylase, Cyp7a1
glucocorticoid receptor, GR
bile acids, BAs
Cell Biology
11β-hydroxysteroid dehydrogenase 1, 11β-HSD1
11β-Hydroxysteroid dehydrogenase
short heterodimer partner, Shp
Bile acids
BA coenzyme A: amino acid N-acyltransferase, Baat
Endocrinology
030220 oncology & carcinogenesis
Organic anion-transporting polypeptide, Oatp
Knockout mouse
Farnesoid X receptor
Original Article
sterol-regulatory element-binding protein 1C, Srebp1c
Organic solute transporter, Ost
hormones, hormone substitutes, and hormone antagonists
Subjects
Details
- Language :
- English
- ISSN :
- 22128778
- Volume :
- 3
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- Molecular Metabolism
- Accession number :
- edsair.doi.dedup.....26df9d3f6d8c1a9201e3253200746132