title: Subcutaneous adipose 11 beta-hydroxysteroid dehydrogenase type 1 activity and messenger ribonucleic acid levels are associated with adiposity and insulinemia in Pima Indians and Caucasians.
abstract: Metabolic effects of cortisol may be critically modulated by glucocorticoid metabolism in tissues. Specifically, active cortisol is regenerated from inactive cortisone by the enzyme 11 beta-hydroxysteroid dehydrogenase type 1 (11-HSD1) in adipose and liver. We examined activity and mRNA levels of 11-HSD1 and tissue cortisol and cortisone levels in sc adipose tissue biopsies from 12 Caucasian (7 males and 5 females) and 19 Pima Indian (10 males and 9 females) nondiabetic subjects aged 28 +/- 7.6 yr (mean +/- SD; range, 18-45). Adipose 11-HSD1 activity and mRNA levels were highly correlated (r = 0.51, P = 0.003). Adipose 11-HSD1 activity was positively related to measures of total (body mass index, percentage body fat) and central (waist circumference) adiposity (P < 0.05 for all) and fasting glucose (r = 0.43, P = 0.02), insulin (r = 0.60, P = 0.0005), and insulin resistance by the homeostasis model (r = 0.70, P < 0.0001) but did not differ between sexes or ethnic groups. Intra-adipose cortisol was positively associated with fasting insulin (r = 0.37, P = 0.04) but was not significantly correlated with 11-HSD1 mRNA or activity or with other metabolic variables. In this cross-sectional study, higher adipose 11-HSD1 activity is associated with features of the metabolic syndrome. Our data support the hypothesis that increased regeneration of cortisol in adipose tissue influences metabolic sequelae of human obesity.
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Phoenix, Arizona 85016, USA.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Lindsay
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Wake
authors.forename: Saraswathy
authors.initials: S
authors.lastname: Nair
authors.forename: Joy
authors.initials: J
authors.lastname: Bunt
authors.forename: Dawn E W
authors.initials: DE
authors.lastname: Livingstone
authors.forename: Paska A
authors.initials: PA
authors.lastname: Permana
authors.forename: P Antonio
authors.initials: PA
authors.lastname: Tataranni
authors.forename: Brian R
authors.initials: BR
authors.lastname: Walker
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D000273:Adipose Tissue / Q000201:enzymology*; D000328:Adult; D003348:Cortisone / Q000378:metabolism; D005260:Female; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism*; D007198:Indians, North American; D007328:Insulin / Q000097:blood*; D008297:Male; D009765:Obesity / Q000208:ethnology* / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D040521:Subcutaneous Tissue / Q000201:enzymology; D044465:White People
chemical_list: D007328:Insulin; D012333:RNA, Messenger; D006913:Hydroxysteroid Dehydrogenases; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; C468386:HSD11B1 protein, human; D003348:Cortisone