title: Pegylated human recombinant leptin (PEG-OB) causes additional weight loss in severely energy-restricted, overweight men.
abstract: BACKGROUND
  Increasing evidence suggests that falling leptin concentrations observed during fasting act as a peripheral signal of starvation, which serves to conserve energy in the face of limited reserves. An extension of this hypothesis is that exogenous leptin should affect energy regulation during severe energy restriction.
  
  
  OBJECTIVE
  To explore this hypothesis, we assessed whether elevated leptin concentrations achieved with the use of long-acting pegylated human recombinant leptin [polyethylene glycol-OB protein (PEG-OB)] affected weight loss and changes in body composition, energy expenditure, appetite, and metabolic variables during semistarvation in healthy overweight men.
  
  
  METHODS
  A randomized, double-blind, placebo-controlled study was executed in overweight men with a mean (+/- SEM) age of 34.8 +/- 1.3 y and body mass index (in kg/m2) of 28.8 +/- 0.5. All subjects received weekly treatment with 80 mg PEG-OB (n = 12) or matching placebo (n = 10) for 46 d while their energy intake was reduced to 2.1 MJ/d by means of a very-low-energy diet. Body composition (hydrodensitometry and deuterium dilution), energy expenditure (ventilated hood), and appetite (visual analogue scales) were evaluated at the start and the end of the study. Metabolic variables were measured throughout the study period.
  
  
  RESULTS
  Compared with placebo treatment, treatment with PEG-OB led to significant (P < 0.03) additional weight loss (14.6 +/- 0.8 compared with 11.8 +/- 0.9 kg) and a reduction in appetite (P < 0.05) after 46 d, but the 2 treatment groups did not differ significantly in changes in body composition, energy expenditure, and metabolic variables.
  
  
  CONCLUSIONS
  Our observations support the hypothesis that the decrease in leptin concentrations during starvation increases appetite in humans.
authors.affiliation: Nutrition and Toxicology Research Institute Maastricht, Department of Human Biology, Maastricht University, Maastricht, Netherlands. c.hukshorn@hb.unimaas.nl
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Hukshorn
authors.forename: Margriet S
authors.initials: MS
authors.lastname: Westerterp-Plantenga
authors.forename: Wim H M
authors.initials: WH
authors.lastname: Saris
mesh_terms: D000293:Adolescent; D000328:Adult; D001823:Body Composition; D015992:Body Mass Index; D004038:Diet, Reducing; D004311:Double-Blind Method; D002149:Energy Intake; D004734:Energy Metabolism; D006801:Humans; D020738:Leptin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000178:diet therapy* / Q000188:drug therapy*; D010919:Placebos; D011092:Polyethylene Glycols / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015431:Weight Loss
chemical_list: D020738:Leptin; D010919:Placebos; D011092:Polyethylene Glycols