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

Am J Clin Nutr. 2015 Oct;102(4):807-19. doi: 10.3945/ajcn.115.109173. Epub 2015 Sep 23.

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.

Keywords: MRI; body composition; energy balance; energy expenditure; metabolic adaptation; refeeding; starvation; weight change; weight loss.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological*
  • Adiponectin / blood
  • Adult
  • Basal Metabolism
  • Body Composition
  • Body Mass Index
  • Body Weight
  • C-Peptide / blood
  • Caloric Restriction*
  • Creatinine / blood
  • Energy Metabolism
  • Ghrelin / blood
  • Heart Rate
  • Humans
  • Insulin / blood
  • Insulin / metabolism
  • Insulin Secretion
  • Leptin / blood
  • Male
  • Minnesota
  • Starvation / metabolism*
  • Testosterone / blood
  • Thermogenesis
  • Triiodothyronine / blood
  • Young Adult

Substances

  • Adiponectin
  • C-Peptide
  • Ghrelin
  • Insulin
  • Leptin
  • Triiodothyronine
  • Testosterone
  • Creatinine

Associated data

  • ClinicalTrials.gov/NCT01737034