Leptin levels, leptin receptor gene polymorphisms, and energy metabolism in women.
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.
Wauters
Machteld
M
Department of Diabetology, Metabolism and Clinical Nutrition, University Hospital Antwerp, Belgium.
Considine
Robert V
RV
Chagnon
Monique
M
Mertens
Ilse
I
Rankinen
Tuomo
T
Bouchard
Claude
C
Van Gaal
Luc F
LF
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
D002352:Carrier Proteins; C515448:LEPR protein, human; D020738:Leptin; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin