title: Tissue specific regulation of glucocorticoids in severe obesity and the response to significant weight loss following bariatric surgery (BARICORT).
abstract: BACKGROUND
  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.
authors.affiliation: Education and Research Centre (C.P.W., M.C., G.G., A.E.H., J.O., D.O., M.S.), St Vincent's University Hospital and St Columcille's Hospital, Dublin, Ireland; Centre for Endocrinology (L.G., A.T., B.H., K.M., J.T., M.S.), Diabetes and Metabolism, Institute of Biomedical Research, University of Birmingham, United Kingdom; Department of Endocrinology (P.M.S.), University of Leeds, Leeds, United Kingdom; and Department of Endocrinology (M.S.), Tallaght Hospital, Dublin and Trinity College, Dublin, Ireland.
authors.forename: C P
authors.initials: CP
authors.lastname: Woods
authors.forename: M
authors.initials: M
authors.lastname: Corrigan
authors.forename: L
authors.initials: L
authors.lastname: Gathercole
authors.forename: A
authors.initials: A
authors.lastname: Taylor
authors.forename: B
authors.initials: B
authors.lastname: Hughes
authors.forename: G
authors.initials: G
authors.lastname: Gaoatswe
authors.forename: K
authors.initials: K
authors.lastname: Manolopoulos
authors.forename: A E
authors.initials: AE
authors.lastname: Hogan
authors.forename: J
authors.initials: J
authors.lastname: O'Connell
authors.forename: P M
authors.initials: PM
authors.lastname: Stewart
authors.forename: J W
authors.initials: JW
authors.lastname: Tomlinson
authors.forename: D
authors.initials: D
authors.lastname: O'Shea
authors.forename: M
authors.initials: M
authors.lastname: Sherlock
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000368:Aged; D050110:Bariatric Surgery; D016022:Case-Control Studies; D005260:Female; D005938:Glucocorticoids / Q000378:metabolism* / Q000652:urine; D006801:Humans; D008297:Male; D017551:Microdialysis; D008875:Middle Aged; D009767:Obesity, Morbid / Q000235:genetics / Q000378:metabolism* / Q000601:surgery* / Q000652:urine; D009928:Organ Specificity; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism; D050151:Subcutaneous Fat / Q000737:chemistry / Q000378:metabolism; D015431:Weight Loss / Q000502:physiology*
chemical_list: D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1