The Gln223Arg polymorphism of the leptin receptor in Pima Indians: influence on energy expenditure, physical activity and lipid metabolism.
Leptin regulates body weight by its receptor-mediated anorectic, thermogenic and antisteatotic effects. Recently, lower leptin binding to the soluble form of the leptin receptor (LEPR) was shown in carriers of the Arg223-encoding allele of the Gln223Arg polymorphism of the LEPR. To investigate whether this variant influences energy metabolism and adiposity in Pima Indians, we genotyped non-diabetic Pima Indians in whom we had measured body composition and 24 h energy expenditure (24 h EE), physical activity level (PAL) and 24 h respiratory quotient (24 h RQ) in a respiratory chamber (n=268) and who had undergone percutaneous fat biopsies from the periumbilical region (n=184). Genotype was not associated with percent body fat (P>0.39), but was associated with 24 h EE, PAL and mean subcutaneous abdominal adipocyte size (SAAS all P<0.05). Homozygotes for the Arg223-encoding allele had lower 24 h EE (P=0.04) and PAL (P=0.007), but larger SAAS (P=0.01) than Gln homozygotes. These findings are consistent with a role of the Gln223Arg polymorphism in reducing peripheral and central leptin binding to the LEPR in humans. However, these effects do not seem to have a major impact on adiposity in this population.
Stefan
N
N
Clinical Diabetes and Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona 85016, USA. nstefan@mail.nih.gov
Vozarova
B
B
Del Parigi
A
A
Ossowski
V
V
Thompson
D B
DB
Hanson
R L
RL
Ravussin
E
E
Tataranni
P A
PA
D017667:Adipocytes / Q000166:cytology; D000328:Adult; D048429:Cell Size; D004734:Energy Metabolism / Q000235:genetics*; D005260:Female; D005838:Genotype; D006720:Homozygote; D006801:Humans; D007198:Indians, North American / Q000235:genetics*; D050356:Lipid Metabolism; D008297:Male; D009043:Motor Activity / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000235:genetics*; D054411:Receptors, Leptin
C515448:LEPR protein, human; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin