Reduced 11β-hydroxysteroid dehydrogenase type 1 activity in obese boys

Abstract

Objective: The incidence of childhood obesity and type 2 diabetes has reached epidemic proportions. Glucocorticoid excess causes central obesity and diabetes mellitus as seen in Cushing's syndrome. The 11b-hydroxysteroid dehydrogenase type 1 enzyme (11b-HSD1) regenerates active cortisol from inactive cortisone. Altered 11b-HSD1 may cause tissue-specific Cushing's syndrome with central obesity and impaired glucose homeostasis. Design, patients, and methods: Clinical and laboratory characteristics, and anthropometric measurements were determined in 15 male and 6 female obese pubertal children (aged 12-18 years, Tanner stages 2-5). In addition, analyses of 24-h excretion rates of glucocorticoids were also performed in 21 age-, sex-, and pubertal stage-matched non-obese children using gas chromatographic-mass spectrometric (GC-MS) analysis. Results: 11b-HSD1 activity (urinary tetrahydrocortisol (THF)C5a-THF/tetrahydrocortisone (THE) ratio) was lower in obese when compared with non-obese boys. In addition, obese children had a higher total cortisol metabolite excretion than non-obese children. 11b-HSD1 activity was significantly related to age in lean and obese children. Standard deviation score (SDS)-body mass index did not correlate with 11b-HSD1 activity, or with total cortisol metabolite excretion within each group. In obese children, 11b-HSD1 activity and total cortisol metabolite excretion showed no correlation to waist-to-hip ratio, fat mass (percentage of body mass), or the homeostasis model assessment of insulin resistance index. Conclusions: In conclusion, our findings strongly suggest that 11b-HSD1 activity increases with age, and is reduced in obese boys. In addition, obese children have a higher total cortisol metabolites excretion suggesting a stimulated hypothalamus-pituitary-adrenal axis.

A gene variant of 11β-hydroxysteroid dehydrogenase type 1 is associated with obesity in children

“…Lower hepatic 11b-HSD1 activity (assessed by the urinary tetrahydrocortisol þ 5a-tetrahydrocortisol/tetrahydrocortisone ratio) has been reported in obese children 28 and is supported by the finding that the activation of oral cortisone to cortisol is impaired in obesity. 5 However, there is no consensus on plasma cortisol levels in obese subjects.…”

Steroid Hormone Profiles in Prepubertal Obese Children Before and After Weight Loss

“…This process may be of particular relevance in central obesity due to 11␤-HSD1 activity in the omental fat tissue (32). However, Wiegand et al (33) reported that 11␤-HSD1 activity is reduced in obese boys. In our study, we did not find a significant relationship between waist circumference and cortisol or cortisone.…”

Expression and Activity of 11β-Hydroxysteroid Dehydrogenase Type 1 Enzyme in Subcutaneous and Visceral Adipose Tissue of Prepubertal Children

“…Wiegand et al[ 14] studied 11β-HSD1 activity and total cortisol metabolite excretion in obese children aged 12–18 years. 11β-HSD1 activity and total cortisol metabolite excretion showed no correlation with waist–hip ratio, fat mass (percentage of body mass), or the homeostasis model assessment of insulin resistance index.…”

“…The authors suggested that 11β-HSD1 activity increases with age, and is reduced in obese boys. In addition, obese children had a higher total cortisol metabolite excretion suggesting increased activation of the hypothalamic-pituitary-adrenal axis [14]. Lean adult women have lower 11β-HSD1 gene expression in SC compared with men, whereas no significant difference was found between obese men and women.…”