Woods, Conor and Corrigan, Michelle and Gathercole, L. and Taylor, A. and Hughes, B. and Gaoatswe, Gadintshware and Manolopoulos, K. and Hogan, Andrew E. and O'Connell, Jean and Stewart, P.M. and Tomlinson, J.W. and O'Shea, Donal and Sherlock, M. (2015) Tissue Specific Regulation of Glucocorticoids in Severe Obesity and the Response to Significant Weight Loss Following Bariatric Surgery (BARICORT). Journal of Clinical Endocrinology and Metabolism, 100 (4). pp. 1434-1444. ISSN 0021-972X

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Abstract

Context: Tissue cortisol exposure is under the control of the isozymes of 11β-hydroxysteroid dehydrogenase (11β-HSD). 11β-HSD1 in vivo, acts as an oxoreductase converting inactive cortisone to active cortisol. We hypothesized that 11β-HSD1 activity is dysregulated in obesity and alters following bariatric surgery induced weight loss in different tissues. Methods: We recruited 21 patients prior to undergoing bariatric surgery and performed cortisol generation profiles (following oral cortisone administration), urinary corticosteroid metabolite analysis, adipose tissue microdialysis, and tissue gene expression before and after weight loss, following bariatric surgery. Archived tissue samples from 20 previous bariatric surgery patients were also used for tissue gene expression studies. Results: Gene expression showed a positive correlation with 11β-HSD1 and BMI in omental adipose tissue (OM) (r = +0.52, P = .0001) but not sc adipose tissue (r = +0.28, P = .17). 11β-HSD1 expression in liver negatively correlated with body mass index (BMI) (r = −0.37, P = .04). 11β-HSD1 expression in sc adipose tissue was significantly reduced after weight loss (0.41 ± 0.28 vs 0.17 ± 0.1 arbitrary units, P = .02). Following weight loss, serum cortisol generation increased during a cortisol generation profile (area under the curve 26 768 ± 16 880 vs 47 579 ± 16 086 nmol/L/minute, P ≤ .0001.) Urinary corticosteroid metabolites demonstrated a significant reduction in total cortisol metabolites after bariatric surgery (15 224 ± 6595 vs 8814 ± 4824 μg/24 h, P = .01). Microdialysis of sc adipose tissue showed a threefold reduction in cortisol/cortisone ratio after weight loss. Conclusions: This study highlights the differences in tissue specific regulation of cortisol metabolism in obesity and after weight loss. Following bariatric surgery hepatic 11β-HSD1 activity increases, sc adipose tissue 11β-HSD1 activity is reduced and total urinary cortisol metabolites are reduced indicating a possible reduction in hypothalamic pituitary adrenal axis drive. 11β-HSD1 expression correlates positively with BMI in omental adipose tissue and negatively within hepatic tissue. 11β-HSD1 expression is reduced in sc adipose tissue after weight loss.

Item Type:	Article
Keywords:	Tissue; Regulation; Glucocorticoids; Obesity; Weight Loss; Bariatric Surgery; BARICORT;
Academic Unit:	Faculty of Science and Engineering > Biology
Item ID:	12419
Identification Number:	https://doi.org/10.1210/jc.2014-4120
Depositing User:	Andrew Hogan
Date Deposited:	17 Feb 2020 14:58
Journal or Publication Title:	Journal of Clinical Endocrinology and Metabolism
Publisher:	Oxford University Press
Refereed:	Yes
URI:	Publisher
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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