title: Leptin levels, leptin receptor gene polymorphisms, and energy metabolism in women.
abstract: OBJECTIVE
  Resting metabolic rate (RMR) is mainly determined by fat-free mass and additionally by age, sex, hormones, and possibly genetic differences. We evaluated whether leptin levels and polymorphisms in the leptin receptor (LEPR) gene were associated with energy expenditure phenotypes.
  
  
  METHODS
  RMR, body composition, and leptin levels were measured in 125 overweight and obese women. Three LEPR polymorphisms, Lys109Arg, Gln223Arg, and Lys656Asn, were typed on genomic DNA of another group of 192 women in whom RMR was measured. Fat, protein, and carbohydrate oxidation were calculated for 103 of these subjects. In 38 subjects, glucose-induced thermogenesis was measured over 3 hours.
  
  
  RESULTS
  In the first study group, a negative correlation between RMR and leptin levels was found after controlling for fat and fat-free mass. In multiple regression analysis, leptin contributed significantly to RMR, independent of body composition. In the second study group, RMR was not associated with LEPR polymorphisms. Differences in substrate oxidation rates were found among genotypes at the Lys656Asn site. In fasting conditions, Lys656Lys showed a trend to oxidize more carbohydrates and less fat than Asn656 carriers, a trend which became significant after the glucose load when carbohydrate oxidation rate in Lys656Lys was 15% higher than in Asn656 carriers (p = 0.04), and fat oxidation rate was 44% lower (p = 0.02).
  
  
  CONCLUSIONS
  These results suggest that DNA sequence variations in the LEPR gene could affect substrate oxidation. We hypothesize that this might be caused by differences in glucose levels, leading to differences in glucose oxidation rates.
authors: Department of Diabetology, Metabolism and Clinical Nutrition, University Hospital Antwerp, Belgium.
authors: Machteld
authors: M
authors: Wauters
authors: Robert V
authors: RV
authors: Considine
authors: Monique
authors: M
authors: Chagnon
authors: Ilse
authors: I
authors: Mertens
authors: Tuomo
authors: T
authors: Rankinen
authors: Claude
authors: C
authors: Bouchard
authors: Luc F
authors: LF
authors: Van Gaal
mesh_terms: D000293:Adolescent; D000328:Adult; D001481:Basal Metabolism; D001823:Body Composition; D015992:Body Mass Index; D002352:Carrier Proteins / Q000235:genetics*; D004734:Energy Metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D020738:Leptin / Q000097:blood*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D012044:Regression Analysis; D022722:Thermogenesis
chemical_list: D002352:Carrier Proteins; C515448:LEPR protein, human; D020738:Leptin; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin