title: Changes in adipose glucocorticoid metabolism before and after bariatric surgery assessed by direct hormone measurements.
abstract: OBJECTIVE
  Increased intra-adipose cortisol is thought to promote obesity, but few human studies have investigated intra-adipose glucocorticoid hormones and none have demonstrated prospective changes with fat loss.
  
  
  METHODS
  Subcutaneous adipose tissue (SAT) was obtained from obese subjects before and 1-year after surgery-induced fat loss, and from nonobese controls. In a second similar cohort of obese subjects, adipocytes and stromal-vascular fraction were isolated. Intra-adipose cortisol and cortisone levels were analyzed by liquid chromatography mass spectrometry and HSD11B1/HSD11B2 mRNA by qPCR.
  
  
  RESULTS
  SAT cortisol/cortisone ratio before fat loss, median 4.8 (interquartile range, 4.1-5.7), was higher than after fat loss, 1.9 (1.0-2.7) (P = 0.001), and compared to nonobese controls, 3.2 (2.4-3.9) (P = 0.005). Cortisone before fat loss, 2.3 (1.2-2.9) nmol/kg, was lower than after fat loss, 5.8 (3.0-10.2) nmol/kg (P = 0.042), and compared to controls, 5.1 (3.8-6.7) nmol/kg (P = 0.013). HSD11B1 was predominantly expressed in mature adipocytes, whereas HSD11B2 was expressed at a higher level in stromal-vascular fraction.
  
  
  CONCLUSIONS
  The intra-adipose glucocorticoid metabolism was markedly altered in the extremely obese state with increased cortisol levels relative to cortisone, whereas fat loss restored this balance approximating nonobese subjects. Changes were more pronounced for cortisone than cortisol, suggesting an adaptive response to insufficient intra-adipose cortisol levels in obesity.
authors.affiliation: Department of Clinical Science, University of Bergen, Bergen, Norway; Hormone Laboratory, Haukeland University Hospital, Bergen, Norway.
authors.forename: Paal
authors.initials: P
authors.lastname: Methlie
authors.forename: Simon
authors.initials: S
authors.lastname: Dankel
authors.forename: Tone
authors.initials: T
authors.lastname: Myhra
authors.forename: Bjørn
authors.initials: B
authors.lastname: Christensen
authors.forename: Jennifer
authors.initials: J
authors.lastname: Gjerde
authors.forename: Dag
authors.initials: D
authors.lastname: Fadnes
authors.forename: Villy
authors.initials: V
authors.lastname: Våge
authors.forename: Kristian
authors.initials: K
authors.lastname: Løvås
authors.forename: Gunnar
authors.initials: G
authors.lastname: Mellgren
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000235:genetics / Q000378:metabolism; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000235:genetics / Q000378:metabolism; D017667:Adipocytes / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D050110:Bariatric Surgery; D015992:Body Mass Index; D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003348:Cortisone / Q000097:blood*; D005260:Female; D005938:Glucocorticoids / Q000378:metabolism*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism / Q000601:surgery; D011446:Prospective Studies; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D005938:Glucocorticoids; D012333:RNA, Messenger; D014280:Triglycerides; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; C468386:HSD11B1 protein, human; C468387:HSD11B2 protein, human; D003348:Cortisone; D006854:Hydrocortisone