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First published September 23, 2015, doi: 10.3945/ajcn.115.109173 Am J Clin Nutr October 2015 vol. 102 no. 4 807-819
Metabolic adaptation to caloric restriction and subsequent refeeding: the Minnesota Starvation Experiment revisited1,2
Manfred James Müller3,*, Janna Enderle3, Maryam Pourhassan3, Wiebke Braun3, Benjamin Eggeling3, Merit Lagerpusch3, Claus-Christian Glüer4, Joseph J Kehayias5, Dieter Kiosz3, and Anja Bosy-Westphal6
Abstract
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 −50% 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), −6.0 kg (CR), and +3.5 kg (refeeding). CR reduced fat mass and FFM by 114 and 159 g/d, respectively. Within FFM, skeletal muscle (−5%), liver (−13%), and kidneys (−8%) decreased. CR also led to reductions in REE (−266 kcal/d), respiratory quotient (−15%), heart rate (−14%), blood pressure (−7%), creatinine clearance (−12%), energy cost of walking (−22%), activity of the sympathetic nervous system (SNS) (−38%), and plasma leptin (−44%), insulin (−54%), adiponectin (−49%), 3,5,3′-tri-iodo-thyronine (T3) (−39%), and testosterone (−11%). 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 = −0.90, 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.
Metabolic adaptation to caloric restriction and subsequent refeeding: the Minnesota Starvation Experiment revisited1,2
Manfred James Müller3,*, Janna Enderle3, Maryam Pourhassan3, Wiebke Braun3, Benjamin Eggeling3, Merit Lagerpusch3, Claus-Christian Glüer4, Joseph J Kehayias5, Dieter Kiosz3, and Anja Bosy-Westphal6
Abstract
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 −50% 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), −6.0 kg (CR), and +3.5 kg (refeeding). CR reduced fat mass and FFM by 114 and 159 g/d, respectively. Within FFM, skeletal muscle (−5%), liver (−13%), and kidneys (−8%) decreased. CR also led to reductions in REE (−266 kcal/d), respiratory quotient (−15%), heart rate (−14%), blood pressure (−7%), creatinine clearance (−12%), energy cost of walking (−22%), activity of the sympathetic nervous system (SNS) (−38%), and plasma leptin (−44%), insulin (−54%), adiponectin (−49%), 3,5,3′-tri-iodo-thyronine (T3) (−39%), and testosterone (−11%). 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 = −0.90, 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.
