BACKGROUND: Diet-induced weight loss is accompanied by adaptive thermogenesis, i.e. a disproportional reduction of resting energy expenditure (REE) a decrease in physical activity and increased movement economy. OBJECTIVE: To determine if energy restriction induced adaptive thermogenesis and adaptations in physical activity are related to changes in leptin concentrations. METHODS: Eighty-two healthy subjects (23 men, 59 women), mean +/- SD age 41 +/- 8 years and BMI 31.9 +/- 3.0 kg/m(2), followed a very low energy diet for 8 weeks with measurements before and after the diet. Leptin concentrations were determined from fasting blood plasma. Body composition was assessed with a three-compartment model based on body weight, total body water (deuterium dilution) and body volume (BodPod). REE was measured (REEm) with a ventilated hood and predicted (REEp) from measured body composition. Adaptive thermogenesis was calculated as REEm/REEp. Parameters for the amount of physical activity were total energy expenditure expressed as a multiple of REEm (PAL), activity-induced energy expenditure divided by body weight (AEE/kg) and activity counts measured by a tri-axial accelerometer. Movement economy was calculated as AEE/kg (MJ/kg/d) divided by activity counts (Mcounts/d). RESULTS: Subjects lost on average 10.7 +/- 4.1% body weight (P<0.001). Leptin decreased from 26.9 +/- 14.3 before to 13.9 +/- 11.3 mug/l after the diet (P<0.001). REEm/REEp after the diet (0.963 +/- 0.08) was related to changes in leptin levels (R(2)=0.06; P<0.05). There was no significant correlation between changes in leptin concentrations and changes in amount of physical activity. Movement economy changed from 0.036 +/- 0.011 J/kg/count to 0.028 +/- 0.010 J/kg/count and was correlated to the changes in leptin concentrations (R(2)=0.07; P<0.05). CONCLUSION: During energy restriction, the decrease in leptin explains part of the variation in adaptive thermogenesis. Changes in leptin are not related to the amount of physical activity but could partly explain the increased movement economy.