11beta-hydroxysteroid dehydrogenase type 1 of the subcutaneous adipose tissue is dysregulated but not associated with metabolic disorders in adults born small for gestational age

Abstract

Introduction: The mechanisms relating being born small for gestational age (SGA) and the later risk of metabolic disorders are not yet fully understood. Adipose 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) activity and expression have been positively associated with metabolic syndrome. In humans, no in vivo studies have explored 11beta-HSD1 activity and gene expression in sc adipose tissue of SGA subjects.

Subjects and methods: Thirty-nine subjects SGA (birth weight<10th percentile) were matched on gender and age with 36 subjects born appropriate for gestational age (AGA) (25th percentile<birth weight<75th percentile); the two groups were stratified according to body fat content into low-fat-mass (20 SGA and 18 AGA) and high-fat-mass (19 SGA and 18 AGA) subjects. Basal and stimulated activities of the 11beta-HSD1 enzyme were assessed in the effluent of microdialysis performed in the abdominal sc wall in vivo. mRNA expression was measured by real-time quantitative PCR.

Results: Basal 11beta-HSD1 activity was comparable in both groups, whereas stimulated activity was lower in SGA subjects. A significant effect of body fat content on the stimulated 11beta-HSD1 activity was found in AGA but not in SGA subjects. 11beta-HSD1 expression was associated with body fat but not with birth weight.

Conclusion: The in vivo stimulated 11beta-HSD1 activity was decreased in subjects born SGA as compared with adults born AGA. 11beta-HSD1 gene expression was not associated with birth weight. It is therefore unlikely that local glucocorticoid metabolism in sc fat plays a major role in the development of the metabolic complications associated with being born SGA.