title: Metabolic adaptation to caloric restriction and subsequent refeeding: the Minnesota Starvation Experiment revisited.
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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Human Nutrition and Food Science and mmueller@nutrfoodsc.uni-kiel.de.
authors.forename: Manfred James
authors.initials: MJ
authors.lastname: Müller
authors.affiliation: Institute of Human Nutrition and Food Science and.
authors.forename: Janna
authors.initials: J
authors.lastname: Enderle
authors.affiliation: Institute of Human Nutrition and Food Science and.
authors.forename: Maryam
authors.initials: M
authors.lastname: Pourhassan
authors.affiliation: Institute of Human Nutrition and Food Science and.
authors.forename: Wiebke
authors.initials: W
authors.lastname: Braun
authors.affiliation: Institute of Human Nutrition and Food Science and.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Eggeling
authors.affiliation: Institute of Human Nutrition and Food Science and.
authors.forename: Merit
authors.initials: M
authors.lastname: Lagerpusch
authors.affiliation: Clinic of Radiology and Neuroradiology, Biomedical Imaging, Molecular Imaging North Competence Centre, University Medical Center Schleswig Holstein, Christian-Albrechts University, Kiel, Germany;
authors.forename: Claus-Christian
authors.initials: CC
authors.lastname: Glüer
authors.affiliation: the Body Composition Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA; and.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Kehayias
authors.affiliation: Institute of Human Nutrition and Food Science and.
authors.forename: Dieter
authors.initials: D
authors.lastname: Kiosz
authors.affiliation: Institute of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Bosy-Westphal
mesh_terms: D000222:Adaptation, Physiological; D052242:Adiponectin / Q000097:blood; D000328:Adult; D001481:Basal Metabolism; D001823:Body Composition; D015992:Body Mass Index; D001835:Body Weight; D002096:C-Peptide / Q000097:blood; D031204:Caloric Restriction; D003404:Creatinine / Q000097:blood; D004734:Energy Metabolism; D054439:Ghrelin / Q000097:blood; D006339:Heart Rate; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D020738:Leptin / Q000097:blood; D008297:Male; D008910:Minnesota; D013217:Starvation / Q000378:metabolism*; D013739:Testosterone / Q000097:blood; D022722:Thermogenesis; D014284:Triiodothyronine / Q000097:blood; D055815:Young Adult
chemical_list: D052242:Adiponectin; D002096:C-Peptide; D054439:Ghrelin; D007328:Insulin; D020738:Leptin; D014284:Triiodothyronine; D013739:Testosterone; D003404:Creatinine
keywords: MRI; body composition; energy balance; energy expenditure; metabolic adaptation; refeeding; starvation; weight change; weight loss