title: The fall in leptin concentration is a major determinant of the metabolic adaptation induced by caloric restriction independently of the changes in leptin circadian rhythms.
abstract: BACKGROUND
  Leptin is involved in the hormonal regulation of the reproductive, somatotropic, thyroid, and autonomic axes and ultimately in the regulation of energy balance. In parallel to the metabolic adaptation observed in response to caloric restriction (CR), plasma leptin concentrations are substantially decreased, suggesting a role for this hormone in the drop in energy expenditure beyond that predicted by the changes in body composition (metabolic adaptation).
  
  
  OBJECTIVE
  The aim of the study was to explore the changes in 24-h leptin circadian rhythm in response to CR and to investigate the relationship between these changes and metabolic adaptation.
  
  
  METHODS
  In a randomized, controlled trial (Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy), 48 subjects were assigned to a control group or one of three CR groups for 6 months. Leptin concentration was assessed every 30 min for 24 h, and leptin circadian variations were fitted by Cosinor analysis. Sedentary energy expenditure and urinary catecholamine excretion were measured for 24 h in a metabolic chamber.
  
  
  RESULTS
  Six months of CR decreased body weight by -11.4 ± 0.6% (mean ± sem; P < 0.001). Mean 24-h circulating leptin concentration decreased by -44 ± 3% (P < 0.001), whereas leptin diurnal amplitude slightly increased over the 6 months of CR. CR caused a metabolic adaptation of -126 ± 25 kcal/d (P <0.001) and a significant decrease in urinary norepinephrine (-13 ± 3%) and T(3) concentrations (10 ± 2%). The metabolic adaptation was significantly and independently related to the changes in 24-h leptin (r(2) = 0 .22, P < 0.01) but not to the changes in leptin amplitude.
  
  
  CONCLUSIONS
  Our results confirm an important role for leptin as an independent determinant of the metabolic adaptation in response to CR.
authors.affiliation: Pennington Biomedical Research Center, 6400 Perkins Road, Baton Rouge, Louisiana 70808, USA.
authors.forename: Virgile
authors.initials: V
authors.lastname: Lecoultre
authors.forename: Eric
authors.initials: E
authors.lastname: Ravussin
authors.forename: Leanne M
authors.initials: LM
authors.lastname: Redman
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology*; D001823:Body Composition / Q000502:physiology; D031204:Caloric Restriction; D002395:Catecholamines / Q000652:urine; D002940:Circadian Rhythm / Q000502:physiology*; D002149:Energy Intake; D004734:Energy Metabolism / Q000502:physiology*; D005260:Female; D006801:Humans; D020738:Leptin / Q000097:blood*; D008297:Male
chemical_list: D002395:Catecholamines; D020738:Leptin