Inhibition of 11β-hydroxysteroid dehydrogenase type 1 reduces food intake and weight gain but maintains energy expenditure in diet-induced obese mice

Abstract

The 11beta-hydroxysteroid dehydrogenase type-1 inhibitor BVT.2733 lowers blood glucose and insulin in mutant mouse models of obesity and diabetes. Its effects on energy balance and body composition, and their contribution to improved glucose homeostasis have received little attention. BVT.2733 (100 mg/kg, orally) was given twice daily to lean and diet-induced obese mice for 16 or 17 days. A group of obese mice was pair-fed to the amounts consumed by BVT.2733-treated mice. In both obese and lean mice, BVT.2733 reduced food intake and weight gain, but increased water intake. Pair-feeding caused almost as great a decrease in body weight as BVT.2733. Energy expenditure was 38+/-8% higher in the BVT.2733-treated obese mice than in the pair-fed mice. Terminal plasma corticosterone was raised, lean body weight reduced and percentage fat unchanged in the pair-fed mice (control, 47.8+/-2.6%; pair-fed, 47.1+/-1.9%), whereas BVT.2733 did not reduce lean mass, but did reduce percentage fat (40.9+/-2.0%). BVT.2733 but not pair-feeding reduced both the glucose tolerance AUC and the plasma insulin concentration 30 min after giving glucose. BVT.2733 reduced food intake but prevented a concomitant reduction in lean body mass and energy expenditure. The latter effects may have contributed to improved glucose tolerance.