The role of glucocorticoid metabolism in bile acid homeostasis

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Main Authors: Opiyo, Monica Naomi, Kenyon, Christopher, Manwani, Kajal, Seckl, Jonathan, Andrew, Ruth, Chapman, Karen E.
Format: Article
Language:English
Published: Endocrine Abstracts, 34 2022
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Online Access:https://repository.daystar.ac.ke/handle/123456789/3960
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author Opiyo, Monica Naomi
Kenyon, Christopher
Manwani, Kajal
Seckl, Jonathan
Andrew, Ruth
Chapman, Karen E.
author_facet Opiyo, Monica Naomi
Kenyon, Christopher
Manwani, Kajal
Seckl, Jonathan
Andrew, Ruth
Chapman, Karen E.
author_sort Opiyo, Monica Naomi
collection DSpace
description Abstract
format Article
id ir-123456789-3960
institution Daystar University
language English
publishDate 2022
publisher Endocrine Abstracts, 34
record_format dspace
spelling ir-123456789-39602024-08-06T07:47:12Z The role of glucocorticoid metabolism in bile acid homeostasis Opiyo, Monica Naomi Kenyon, Christopher Manwani, Kajal Seckl, Jonathan Andrew, Ruth Chapman, Karen E. Glucocorticoid metabolism Bile acid homeostasis Abstract Background and aims: Bile acids are conserved through enterohepatic circulation, a glucocorticoid-modulated process. 11β-Hydroxysteroid dehydrogenase type-1 (11β-HSD1) converts cortisone/11-dehydrocortisone to cortisol/corticosterone, thus increasing intracellular glucocorticoid levels. 11β-HSD1 also metabolises 7-oxo-lithocholic acid, a bile acid. 11β-HSD1 is highly expressed in the liver and may alter bile acid transport through regeneration of active glucocorticoids or may directly metabolise bile acids, thus altering profile. We compared bile acid synthesis, release, their enterohepatic circulation and profile in Hsd11b1−/− and isogenic C57Bl/6 control mice. Methods: Adult male, chow-fed mice (eight per group) were fasted for 4 h or fasted for 4 h then re-fed 4 h. Serum, and liver and gall-bladder bile acid concentrations and profiles were measured by spectrophotometry/gas chromatography–mass spectrometry. Results: Fasted Hsd11b1−/− and C57Bl/6 mice had similar volumes of bile (3.2 vs 5.0 l). 7β-Hydroxylated acids (ω-muricholic>β-muricholic>ursodeoxycholic acid>others) predominated in bile of C57Bl/6 mice while 7α-hydroxylated acids (cholic>α-muricholic>chenodeoxycholic acid>others) predominated in Hsd11b1−/− mice; the ratio of 7α:7β acids was >100 greater in Hsd11b1−/−mice. In fasted Hsd11b1− mice, bile acid concentrations were higher in serum (Hsd11b1−/−: 30±9 vs C57Bl/6: 3.8±1.3 nM, P<0.0001) and liver (Hsd11b1−/−: 243±18 vs C57Bl/6: 139±19 nmol/g, P<0.001). Re-feeding caused gall bladder emptying in C57Bl/6 mice (49.6±8% of fasted weight, P<0.0001) and increased serum (62.5±7.6 nM) and liver (497±20 nmol/g) bile acid concentrations, while in Hsd11b1− mice, the gall bladder did not empty (92±7.8% fasted weight) and serum (24±12 nM) and liver (122±21 nmol/g) bile acid concentrations were similar to the fasted state. Conclusion: Bile acid release and the pattern of synthesis is controlled by 11β-HSD1 activity in mice. This may affect digestion and, depending on functional differences of 7α- and 7β- hydroxylated bile acids, may have significant effects on lipid and sterol metabolism and bile acid-mediated transcription. 2022-07-18T13:39:26Z 2022-07-18T13:39:26Z 2014 Article Opiyo, M. N., Escher, G., Kenyon, C., Seckl, J., Andrew, R., & Chapman, K. (2014). The role of glucocorticoid metabolism in bile acid homeostasis. Endocrine Abstracts, 34. https://doi.org/10.1530/endoabs.34.P252 https://repository.daystar.ac.ke/handle/123456789/3960 en application/vnd.openxmlformats-officedocument.wordprocessingml.document Endocrine Abstracts, 34
spellingShingle Glucocorticoid metabolism
Bile acid homeostasis
Opiyo, Monica Naomi
Kenyon, Christopher
Manwani, Kajal
Seckl, Jonathan
Andrew, Ruth
Chapman, Karen E.
The role of glucocorticoid metabolism in bile acid homeostasis
title The role of glucocorticoid metabolism in bile acid homeostasis
title_full The role of glucocorticoid metabolism in bile acid homeostasis
title_fullStr The role of glucocorticoid metabolism in bile acid homeostasis
title_full_unstemmed The role of glucocorticoid metabolism in bile acid homeostasis
title_short The role of glucocorticoid metabolism in bile acid homeostasis
title_sort role of glucocorticoid metabolism in bile acid homeostasis
topic Glucocorticoid metabolism
Bile acid homeostasis
url https://repository.daystar.ac.ke/handle/123456789/3960
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