Subcutaneous Adipose 11β-Hydroxysteroid Dehydrogenase Type 1 Activity and Messenger Ribonucleic Acid Levels Are Associated with Adiposity and Insulinemia in Pima Indians and Caucasians

• Published in: The journal of clinical endocrinology and metabolism Vol. 88; no. 6; pp. 2738 - 2744
• Main Authors: Lindsay, Robert S., Wake, Deborah J., Nair, Saraswathy, Bunt, Joy, Livingstone, Dawn E. W., Permana, Paska A., Tataranni, P. Antonio, Walker, Brian R.
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 01.06.2003; Copyright Oxford University Press
• Subjects: 11-beta-Hydroxysteroid Dehydrogenase Type 1; Adipose Tissue - enzymology; Adult; Biological and medical sciences; Cortisone - metabolism; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; European Continental Ancestry Group; Female; Humans; Hydroxysteroid Dehydrogenases - genetics; Hydroxysteroid Dehydrogenases - metabolism; Indians, North American; Insulin - blood; Male; Medical sciences; Metabolic diseases; Obesity; Obesity - ethnology; Obesity - metabolism; RNA, Messenger - metabolism; Subcutaneous Tissue - enzymology; Endocrinopathy; Amerindian; Pancreatic hormone; Adipose tissue; Isozyme; Pathogenesis; Cardiovascular disease; Hydrocortisone; Glucocorticoid; Fat mass; Body composition; Messenger RNA; Enzymatic activity; X Syndrome; 11β-Hydroxysteroid dehydrogenase; Adult; Hormonal investigation; Human; Enzyme; Metabolic diseases; Gene expression; Insulin; Cortisone; Adrenal hormone; Oxidoreductases; Caucasoid
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2002-030017

Metabolic effects of cortisol may be critically modulated by glucocorticoid metabolism in tissues. Specifically, active cortisol is regenerated from inactive cortisone by the enzyme 11β-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.