title: Altered metabolic homeostasis is associated with appetite regulation during and following 48-h of severe energy deprivation in adults.
abstract: BACKGROUND
  Military personnel frequently endure intermittent periods of severe energy deficit which can compromise health and performance. Physiologic factors contributing to underconsumption, and the subsequent drive to overeat, are not fully characterized. This study aimed to identify associations between appetite, metabolic homeostasis and endocrine responses during and following severe, short-term energy deprivation.
  
  
  METHODS
  Twenty-three young adults (17M/6F, 21±3years, BMI 25±3kg/m(2)) participated in a randomized, controlled, crossover trial. During separate 48-h periods, participants increased habitual energy expenditure by 1647±345kcal/d (mean±SD) through prescribed exercise at 40-65% VO2peak, and consumed provided isovolumetric diets designed to maintain energy balance at the elevated energy expenditure (EB; 36±93kcal/d energy deficit) or to produce a severe energy deficit (ED; 3681±716kcal/d energy deficit). Appetite, markers of metabolic homeostasis and endocrine mediators of appetite and substrate availability were periodically measured. Ad libitum energy intake was measured over 36h following both experimental periods.
  
  
  RESULTS
  Appetite increased during ED and was greater than during EB despite maintenance of diet volume (P=0.004). Ad libitum energy intake was 907kcal/36h [95% CI: 321, 1493kcal/36h, P=0.004] higher following ED compared to following EB. Serum beta-hydroxybutyrate, free fatty acids, branched-chain amino acids, dehydroepiandrosterone-sulfate (DHEA-S) and cortisol concentrations were higher (P<0.001 for all), whereas whole-body protein balance was more negative (P<0.001), and serum glucose, insulin, and leptin concentrations were lower (P<0.001 for all) during ED relative to during EB. Cortisol concentrations, but not any other hormone or metabolic substrate, were inversely associated with satiety during EB (R(2)=0.23, P=0.04). In contrast, serum glucose and DHEA-S concentrations were inversely associated with satiety during ED (R(2)=0.68, P<0.001). No associations between physiologic variables measured during EB and ad libitum energy intake following EB were observed. However, serum leptin and net protein balance measured during ED were inversely associated with ad libitum energy intake following ED (R(2)=0.48, P=0.01).
  
  
  CONCLUSIONS
  These findings suggest that changes in metabolic homeostasis during energy deprivation modulate appetite independent of reductions in diet volume. Following energy deprivation, physiologic signals of adipose and lean tissue loss may drive restoration of energy balance.
  
  
  BACKGROUND
  www.clinicaltrials.gov #NCT01603550.
authors.affiliation: Military Nutrition Division, US Army Research Institute of Environmental Medicine, 10 General Greene Ave, Bldg 42, Natick, MA 01760, USA. Electronic address: james.p.karl.civ@mail.mil.
authors.forename: J Philip
authors.initials: JP
authors.lastname: Karl
authors.affiliation: Military Nutrition Division, US Army Research Institute of Environmental Medicine, 10 General Greene Ave, Bldg 42, Natick, MA 01760, USA.
authors.forename: Tracey J
authors.initials: TJ
authors.lastname: Smith
authors.affiliation: Military Nutrition Division, US Army Research Institute of Environmental Medicine, 10 General Greene Ave, Bldg 42, Natick, MA 01760, USA.
authors.forename: Marques A
authors.initials: MA
authors.lastname: Wilson
authors.affiliation: Military Nutrition Division, US Army Research Institute of Environmental Medicine, 10 General Greene Ave, Bldg 42, Natick, MA 01760, USA.
authors.forename: Asma S
authors.initials: AS
authors.lastname: Bukhari
authors.affiliation: Military Nutrition Division, US Army Research Institute of Environmental Medicine, 10 General Greene Ave, Bldg 42, Natick, MA 01760, USA.
authors.forename: Stefan M
authors.initials: SM
authors.lastname: Pasiakos
authors.affiliation: Military Nutrition Division, US Army Research Institute of Environmental Medicine, 10 General Greene Ave, Bldg 42, Natick, MA 01760, USA.
authors.forename: Holly L
authors.initials: HL
authors.lastname: McClung
authors.affiliation: Military Nutrition Division, US Army Research Institute of Environmental Medicine, 10 General Greene Ave, Bldg 42, Natick, MA 01760, USA.
authors.forename: James P
authors.initials: JP
authors.lastname: McClung
authors.affiliation: Military Nutrition Division, US Army Research Institute of Environmental Medicine, 10 General Greene Ave, Bldg 42, Natick, MA 01760, USA.
authors.forename: Harris R
authors.initials: HR
authors.lastname: Lieberman
mesh_terms: D015308:Anaerobic Threshold; D001069:Appetite Regulation / Q000502:physiology*; D003071:Cognition / Q000502:physiology; D018592:Cross-Over Studies; D004032:Diet; D002149:Energy Intake / Q000502:physiology*; D004734:Energy Metabolism / Q000502:physiology; D005260:Female; D006706:Homeostasis / Q000502:physiology*; D006728:Hormones / Q000097:blood; D006801:Humans; D008297:Male; D008889:Military Personnel; D010806:Physical Education and Training; D011506:Proteins / Q000378:metabolism; D013217:Starvation / Q000097:blood; D015431:Weight Loss; D055815:Young Adult
chemical_list: D006728:Hormones; D011506:Proteins
keywords: Energy density; Satiety; Starvation; Substrate oxidation; Weight loss