Decreased 11beta-hydroxysteroid dehydrogenase type 1 activity in obese boys
Susanna Wiegand1, Anna Richardt1, Thomas Remer3, Stefan A Wudy4, Jeremy W Tomlinson5, Annette Grüters1, Paul M Stewart5, Christian J Strasburger2 & Marcus Quinkler2
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 Cushings syndrome. The 11beta-hydroxysteroid dehydrogenase type 1 enzyme (11beta-HSD1), which is predominantly expressed in liver and adipose tissue, regenerates active cortisol from inactive cortisone. Increased 11beta-HSD1 may cause tissue-specific Cushing syndrome with central obesity and impaired glucose homeostasis.
Design, patients and methods: Clinical and laboratory characteristics, and anthropometric measurements were determined in 15 male (aged 1218) and 6 female (aged 1218) obese pubertal children. In addition, analysis of 24 h excretion rates of glucocorticoids were performed in obese and age- and sex-matched non-obese children using gas chromatographic-mass spectrometric (GC-MS) analysis.
Results: 11beta-HSD1 activity (urinary THF+5alphaTHF/THE ratio) was lower in obese compared to non-obese boys. In addition, obese children had a higher total cortisol metabolite excretion than non-obese children. 11beta-HSD1 activity was significantly related to age, but not to waist-to-hip ratio, fat mass (% of body mass), or insulin resistance index (HOMA). Standard deviation score (SDS)-BMI did not correlate with 11beta-HSD1 or −2 (urinary free F/ free E ratio) activity, or with total cortisol metabolite excretion. We did not find a gender difference regarding 11beta-HSD1 or −2 activity. 11beta-HSD2 activity significantly correlated to abdominal circumference in obese children.
Conclusions: In conclusion, our findings strongly suggest that 11beta-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 HPA axis.