Metabolic adaptation to caloric restriction and subsequent refeeding: the Minnesota Starvation Experiment revisited.

Background: Adaptive thermogenesis (AT) is the fat-free mass (FFM)-independent reduction of resting energy expenditure (REE) to caloric restriction (CR). AT attenuates weight loss and favors weight regain. Its variance, dynamics, and control remain obscure. Objectives: Our aims were to address the variance and kinetics of AT, its associations with body composition in the context of endocrine determinants, and its effect on weight regain. Design: Thirty-two nonobese men underwent sequential overfeeding (1 wk at +50% of energy needs), CR (3 wk at 250% of energy needs), and refeeding (2 wk at +50% of energy needs). AT and its determinants were measured together with body composition as assessed with the use of quantitative magnetic resonance, whole-body MRI, isotope dilution, and nitrogen and fluid balances. Results: Changes in body weight were +1.8 kg (overfeeding), 26.0 kg (CR), and +3.5 kg (refeeding). CR reduced fat mass and FFM by 114 and 159 g/d, respectively. Within FFM, skeletal muscle (25%), liver (213%), and kidneys (28%) decreased. CR also led to reductions in REE (2266 kcal/d), respiratory quotient (215%), heart rate (214%), blood pressure (27%), creatinine clearance (212%), energy cost of walking (222%), activity of the sympathetic nervous system (SNS) (238%), and plasma leptin (244%), insulin (254%), adiponectin (249%), 3,5,3#-tri-iodo-thyronine (T3) (239%), and testosterone (211%). AT was 108 kcal/d or 48% of the decrease in REE. Changes in FFM composition explained 36 kcal, which left 72 kcal/d for true AT. The decrease in AT became significant at #3 d of CR and was related to decreases in insulin secretion (r = 0.92, P , 0.001), heart rate (r = 0.60, P , 0.05), creatinine clearance (r = 0.79, P , 0.05), negative fluid balance (r = 0.51, P , 0.01), and the free water clearance rate (r = 20.90, P , 0.002). SNS activity and plasma leptin, ghrelin, and T3 and their changes with CR were not related to AT. Conclusion: During early weight loss, AT is associated with a fall in insulin secretion and body fluid balance. This trial was registered at clinicaltrials.gov as NCT01737034. [ABSTRACT FROM AUTHOR]