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.
journal_name
Mol Metabjournal_title
Molecular metabolismauthors
Penno CA,Morgan SA,Rose AJ,Herzig S,Lavery GG,Odermatt Adoi
10.1016/j.molmet.2014.04.008subject
Has Abstractpub_date
2014-05-02 00:00:00pages
554-64issue
5issn
2212-8778pii
S2212-8778(14)00086-6journal_volume
3pub_type
杂志文章abstract:OBJECTIVE:Appetitive responses to weight loss are mediated by a nutrient-sensing neural network comprised of melanocortin neurons. The role of neural melanocortin-3 receptors (MC3R) in mediating these responses is enigmatic. Mc3r knockout mice exhibit a paradoxical phenotype of obesity and reduced feeding-related behav...
journal_title:Molecular metabolism
pub_type: 杂志文章
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journal_title:Molecular metabolism
pub_type: 杂志文章,评审
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journal_title:Molecular metabolism
pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章
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更新日期:2018-05-01 00:00:00
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pub_type: 杂志文章
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更新日期:2016-02-13 00:00:00
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更新日期:2018-06-01 00:00:00
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pub_type: 杂志文章,评审
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更新日期:2016-01-14 00:00:00
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pub_type: 杂志文章,评审
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更新日期:2020-05-01 00:00:00