Indirect calorimetry is increasingly used to investigate why compounds or genetic manipulations affect body weight or composition in small animals. This review introduces the principles of indirect (primarily open-circuit) calorimetry and explains some common misunderstandings. It is not widely understood that in open-circuit systems in which carbon dioxide (CO 2 ) is not removed from the air leaving the respiratory chamber, measurement of airflow out of the chamber and its oxygen (O 2 ) content paradoxically allows a more reliable estimate of energy expenditure (EE) than of O 2 consumption. If the CO 2 content of the exiting air is also measured, both O 2 consumption and CO 2 production, and hence respiratory quotient (RQ), can be calculated. Respiratory quotient coupled with nitrogen excretion allows the calculation of the relative combustion of the macronutrients only if measurements are over a period where interconversions of macronutrients that alter their pool sizes can be ignored. Changes in rates of O 2 consumption and CO 2 production are not instantly reflected in changes in the concentrations of O 2 and CO 2 in the air leaving the respiratory chamber. Consequently, unless air-flow is high and chamber size is small, or rates of change of O 2 and CO 2 concentrations are included in the calculations, maxima and minima are underestimated and will appear later than their real times. It is widely appreciated that bigger animals with more body tissue will expend more energy than smaller animals. A major issue is how to compare animals correcting for such differences in body size. Comparison of the EE or O 2 consumption per gram body weight of lean and obese animals is misleading because tissues vary in their energy requirements or in how they influence EE in other ways. Moreover, the contribution of fat to EE is lower than that of lean tissue. Use of metabolic mass for normalisation, based on interspecific scaling exponents (0.75 or 0.66), is similarly flawed. It is best to use analysis of covariance to determine the relationship of EE to body mass or fat-free mass within each group, and then test whether this relationship differs between groups.

Aims/hypothesis: The 11β-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. Materials and methods: 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. Results: 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 pairfed 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 pairfeeding reduced both the glucose tolerance AUC and the plasma insulin concentration 30 min after giving glucose. Conclusions/interpretation: 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.