To Örebro University

BACKGROUND AND AIMS: The role of 11beta-hydroxysteroid dehydrogenase 1 (11beta-HSD1) in the pathogenesis of obesity has been elucidated in humans and in various rodent models. Obesity is accompanied by disturbances in glucocorticoid metabolism, circulating adipokine levels, and fatty acid (FA) reesterification. This study was undertaken to evaluate glucocorticoid metabolism in sc fat before and after weight loss and to explore putative associations between 11beta-HSD1 and leptin, adiponectin, and FA recycling.

SUBJECTS AND METHODS: Twenty-seven obese (mean body mass index 44.4 + or - 4.4 kg/m(2)) women underwent gastric bypass surgery. Subcutaneous fat biopsies were collected before and 2 yr after surgery. The expression of 11beta-HSD1, leptin, adiponectin, and phosphoenolpyruvate carboxykinase (PEPCK) mRNA was evaluated with real-time PCR. Serum leptin and adiponectin protein levels were estimated by ELISA.

RESULTS: Two years after gastric bypass surgery, significant reductions were observed in the mean body mass index (from 44.4 to 30.8 kg/m(2)) and mean waist circumference (from 121.9 to 90.6 cm). After weight loss, 11beta-HSD1 mRNA expression decreased 4-fold (P < 0.001). Both leptin and adiponectin mRNA expression decreased, with concomitantly decreased circulating leptin and increased circulating adiponectin levels. PEPCK mRNA expression did not change.

CONCLUSION: Weight loss after gastric bypass surgery was followed by metabolically favorable changes in insulin sensitivity, circulating leptin and adiponectin, and peripheral glucocorticoid metabolism. A significant reduction in 11beta-HSD1 expression was observed in sc adipose tissue after weight loss. This suggests that up-regulation of 11beta-HSD1 is a consequence, rather than a cause, of obesity.