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Objective To characterize the contributions of the loss of energy-expending tissues and metabolic adaptations to the reduction in resting metabolic rate (RMR) following weight loss. Methods A secondary analysis was conducted on data from the  Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy  study. Changes in RMR, body composition, and metabolic hormones were examined over 12 months of calorie restriction in 109 individuals. The contribution of tissue losses to the decline in RMR was determined by weighing changes in the size of energy-expending tissues and organs (skeletal muscle, adipose tissue, bone, brain, inner organs, residual mass) assessed by dual-energy X-ray absorptiometry with their tissue-specific metabolic rates. Metabolic adaptations were quantified as the remaining reduction in RMR. Results RMR was reduced by 101 ± 12 kcal/d as participants lost 7.3 ± 0.2 kg (both  p  &lt; 0.001). On average, 60% of the total reduction in RMR were explained by energy-expending tissues losses, while 40% were attributed to metabolic adaptations. The loss of skeletal muscle mass (1.0 ± 0.7 kg) was not significantly related to RMR changes ( r  = 0.14,  p  = 0.16), whereas adipose tissue losses (7.2 ± 3.0 kg) were positively associated with the reduction in RMR ( r  = 0.42,  p  &lt; 0.001) and metabolic adaptations ( r  = 0.31,  p  &lt; 0.001). Metabolic adaptations were correlated with declines in leptin ( r  = 0.27,  p  &lt; 0.01), triiodothyronine ( r  = 0.19,  p  &lt; 0.05), and insulin ( r  = 0.25,  p  &lt; 0.05). Conclusions During weight loss, tissue loss and metabolic adaptations both contribute to the reduction in RMR, albeit variably. Contrary to popularly belief, it is not skeletal muscle, but rather adipose tissue losses that seem to drive RMR reductions following weight loss. Future research should target personalized strategies addressing the predominant cause of RMR reduction for weight maintenance.

Tissue losses and metabolic adaptations both contribute to the reduction in resting metabolic rate following weight loss