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The Gln223Arg polymorphism of the leptin receptor in Pima Indians: influence on energy expenditure, physical activity and lipid metabolism

International Journal of Obesity volume 26, pages 1629–1632 (2002)Cite this article

Abstract

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.

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Acknowledgements

We gratefully acknowledge the help of the nursing and dietary staff for the care of the volunteers. We also thank the technical staff of the NIH Clinical Diabetes and Nutrition Section in Phoenix. Finally, we are grateful to the members and leaders of the Gila River Indian Community for their continuing cooperation in our studies.

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Authors and Affiliations

  1. Clinical Diabetes and Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona, USA

    N Stefan, B Vozarova, A Del Parigi, V Ossowski, DB Thompson & PA Tataranni

  2. Diabetes and Arthritis Epidemiology Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona, USA

    RL Hanson

  3. Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA

    E Ravussin

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  1. N Stefan
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  2. B Vozarova
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  3. A Del Parigi
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  4. V Ossowski
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  5. DB Thompson
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  6. RL Hanson
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  7. E Ravussin
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  8. PA Tataranni
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Correspondence to N Stefan.

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Stefan, N., Vozarova, B., Del Parigi, A. et al. The Gln223Arg polymorphism of the leptin receptor in Pima Indians: influence on energy expenditure, physical activity and lipid metabolism. Int J Obes 26, 1629–1632 (2002). https://doi.org/10.1038/sj.ijo.0802161

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