BACKGROUND: Metabolic adaptation (MA) in response to weight loss is highly variable. Several methodological issues are likely to contribute to the large inter-individual variability in MA, namely the lack of adjustment for changes in the composition of fat-free mass. OBJECTIVE: The aim of this analysis was to investigate the contribution of changes in trunk versus limb lean body mass (LBM) to the variability in MA, at the level of resting metabolic rate (RMR). METHODS: 116 premenopausal women with overweight (body mass index (BMI): 28.2 ± 1.2 kg/m RESULTS: A large variation in MA (-206 to +233 kcal/day) was found after an average of 12.1 ± 2.4 kg weight loss. After adjusting for RMR at baseline and changes in S CONCLUSION: In premenopausal women with overweight and loss of trunk, but not limbs, LBM contributes to MA variability, suggesting that loss of organ mass might be more important than loss of skeletal mass in modulating the magnitude of MA.