Objectives: It has been demonstrated that leptin influences the energy balance by regulating appetite and
increasing energy expenditure (EE). However, the relationship between circulating leptin and EE is confounded owing to variations in body composition. The aim of this study was to determine the role of circulating leptin in energy regulation and to examine whether the leptin-mediated changes in EE are associated
with adiposity among healthy adults living in Singapore.
Methods: We conducted a cross-sectional study of 300 participants (112 men). Resting metabolic rate (RMR)
was measured by indirect calorimetry. Body composition (i.e., fat mass [FM] and fat-free mass [FFM]) was
measured by dual-energy x-ray absorptiometry. Serum leptin levels were determined by radioimmunoassay.
Results: There were strong correlations between circulating leptin levels, FM, and RMR in healthy men and
women. After normalization of RMR by a power function model (kcal¢kg FFM0.86¢d 1
), the influence of FFM
can be effectively removed. The normalized RMR was significantly associated with both FM (r = 0.28, P <
0.001) and log leptin (r = 0.35, P < 0.001). In the stepwise multiple regression analysis, leptin level is the
major predictor for normalized RMR, accounting for 12% of the variation. In contrast, FM did not explain any
variation in normalized RMR.
Conclusion: Leptin may be a more significant predictor of normalized RMR than FM per se. The contribution
of FM to RMR could be via a mechanism that is related to leptin-dependent responses involved in energy