title: Diet-induced weight loss has chronic tissue-specific effects on glucocorticoid metabolism in overweight postmenopausal women.
abstract: OBJECTIVE
  Tissue-specific glucocorticoid metabolism is altered in obesity, and may increase cardiovascular risk. This dysregulation is normalized by short-term calorie restriction and weight loss, an effect that varies with dietary macronutrient composition. However, tissue-specific glucocorticoid metabolism has not been studied during long-term (>6 months) dietary interventions. Therefore our aim was to test whether long-term dietary interventions, either a paleolithic-type diet (PD) or a diet according to Nordic nutrition recommendations (NNR) could normalize tissue-specific glucocorticoid metabolism in overweight and obese women.
  
  
  METHODS
  Forty-nine overweight/obese postmenopausal women were randomized to a paleolithic diet or a diet according to NNR for 24 months. At baseline, 6 and 24 months anthropometric measurements, insulin sensitivity, excretion of urinary glucocorticoid metabolites in 24-hour collections, conversion of orally administered cortisone to plasma cortisol and transcript levels of 11β hydroxysteroid dehydrogenase type 1 (11βHSD1) in subcutaneous adipose tissue were studied.
  
  
  RESULTS
  Both diet groups achieved significant and sustained weight loss. Weight loss with the PD was greater than on NNR diet after 6 months (P<0.001) but similar at 24 months. Urinary measurement of 5α-reductase activity was increased after 24 months in both groups compared with baseline (P<0.001). Subcutaneous adipose tissue 11βHSD1 gene expression decreased at 6 and 24 months in both diet groups (P=0.036). Consistent with increased liver 11βHSD1, conversion of oral cortisone to cortisol increased at 6 months (P=0.023) but was unchanged compared with baseline by 24 months.
  
  
  CONCLUSIONS
  Long-term weight loss in postmenopausal women has tissue-specific and time-dependent effects on glucocorticoid metabolism. This may alter local-tissue cortisol exposure contributing to improved metabolic function during weight loss.
authors.affiliation: Department for Public Health and Clinical Medicine, Medicine, Umeå University, Umeå, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Stomby
authors.affiliation: Department for Public Health and Clinical Medicine, Medicine, Umeå University, Umeå, Sweden.
authors.forename: K
authors.initials: K
authors.lastname: Simonyte
authors.affiliation: Department for Public Health and Clinical Medicine, Medicine, Umeå University, Umeå, Sweden.
authors.forename: C
authors.initials: C
authors.lastname: Mellberg
authors.affiliation: Department for Public Health and Clinical Medicine, Medicine, Umeå University, Umeå, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Ryberg
authors.affiliation: BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, Scotland.
authors.forename: R H
authors.initials: RH
authors.lastname: Stimson
authors.affiliation: 1] Department of Food and Nutrition and Sport Science, University of Gothenburg, Gothenburg, Sweden [2] Department of Food and Nutrition, Umeå University, Umeå, Sweden.
authors.forename: C
authors.initials: C
authors.lastname: Larsson
authors.affiliation: Department for Public Health and Clinical Medicine, Medicine, Umeå University, Umeå, Sweden.
authors.forename: B
authors.initials: B
authors.lastname: Lindahl
authors.affiliation: BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, Scotland.
authors.forename: R
authors.initials: R
authors.lastname: Andrew
authors.affiliation: BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, Scotland.
authors.forename: B R
authors.initials: BR
authors.lastname: Walker
authors.affiliation: 1] Department for Public Health and Clinical Medicine, Medicine, Umeå University, Umeå, Sweden [2] Stellenbosch Institute for Advanced Study (STIAS), Wallenberg Research Centre at Stellenbosch University, Stellenbosch, South Africa.
authors.forename: T
authors.initials: T
authors.lastname: Olsson
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism*; D015992:Body Mass Index; D031204:Caloric Restriction; D002318:Cardiovascular Diseases / Q000378:metabolism / Q000517:prevention & control*; D002149:Energy Intake; D004734:Energy Metabolism; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D007333:Insulin Resistance; D008875:Middle Aged; D050177:Overweight / Q000178:diet therapy* / Q000378:metabolism / Q000517:prevention & control; D017698:Postmenopause / Q000378:metabolism*; D012307:Risk Factors; D016896:Treatment Outcome; D015431:Weight Loss; D061217:Weight Reduction Programs
chemical_list: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D006854:Hydrocortisone