11β-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

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. 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. 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. 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.