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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Tartaglia LA, Dembski M, Weng X, Deng N, Culpepper J, Devos R, Richards GJ, Campfield LA, Clark FT, Deeds J . Identification and expression cloning of a leptin receptor, OB-R Cell 1995 83 7: 1263–1271.
Lee GH, Proenca R, Montez JM, Carroll KM, Darvishzadeh JG, Lee JI, Friedman JM . Abnormal splicing of the leptin receptor in diabetic mice Nature 1996 379 6566: 632–635.
Thompson DB, Ravussin E, Bennett PH, Bogardus C . Structure and sequence variation at the human leptin receptor gene in lean and obese Pima Indians Hum Mol Genet 1997 6 5: 675–679.
Quinton ND, Lee AJ, Ross RJ, Eastell R, Blakemore AI . A single nucleotide polymorphism (SNP) in the leptin receptor is associated with BMI, fat mass and leptin levels in postmenopausal Caucasian woman Hum Genet 2001 108 3: 233–236.
Goldman RF, Buskirk ER . A method for underwater weighing and the determination of body density In: Brozek J, Herschel A (eds) Techniques for measuring body composition National Research Council: Washington, DC 1961 pp 78–106.
Tataranni PA, Ravussin E . Use of dual-energy X-ray absorptiometry in obese individuals Am J Clin Nutr 1995 62 4: 730–734.
Ravussin E, Lillioja S, Anderson TE, Christin L, Bogardus C . Determinants of 24-hour energy expenditure in man. Methods and results using a respiratory chamber J Clin Invest 1986 78 6: 1568–1578.
Snitker S, Tataranni PA, Ravussin E . Spontaneous physical acitivity in a respiratory chamber is correlated to habitual physical activity Int J Obes Relat Metab Disord 2001 25 10: 1481–1486.
Foley JE, Lillioja S, Zawadzki J, Reaven G . Comparison of glucose metabolism in adipocytes from Pima Indians and Caucasians Metabolism 1986 35 2: 193–195.
Zeger SL, Liang KY, Albert PS . Models for longitudinal data: a generalized estimating equation approach Biometrics 1988 44 4: 1049–1060.
Rotnitzky A, Jerell NP . Hypothesis testing of regression parameters in semiparametric generalized linear models for cluster correlated data Biometrika 1990 77: 485–497.
Spiegelman BM, Flier JS . Obesity and the regulation of energy balance Cell 2001 104 4: 531–543.
Nicklas BJ, Toth MJ, Poehlman ET . Daily energy expenditure is related to plasma leptin concentrations in older African-American women but not men Diabetes 1997 46 9: 1389–1392.
Kennedy A, Gettys TW, Watson P, Wallace P, Ganaway E, Pan Q, Garvey WT . The metabolic significance of liptin in humans: gender-based differences in Relationship to adiposity, insulin sensitivity, and energy expenditure J Clin Endocrinol Metab 1997 82 4: 1293–1300.
Tang-Christensen M, Havel PJ, Jacobs RR, Larsen PJ, Cameron JL . Central administration of leptin inhibits food intake and activates the sympathetic nervous system in rhesus macaques J Clin Endocrinol Metab 1999 84 2: 711–717.
Snitker S, Pratley RE, Nocolson M, Tataranni PA, Ravussin E . Relationship between muscle sympathetic nerve activity and plasma leptin concentration Obes Res 1997 5 4: 338–340.
Christin L, O'Connell M, Bogardus C, Danforth E Jr, Ravussin E . Norepinephrine turnover and energy expenditure in Pima Indian and white men Metabolism 1993 42 6: 723–729.
Wang MY, Lee Y, Unger RH . Novel form of lipolysis induced by leptin J Biol Chem 1999 274 25: 17541–17544.
Lemonnier D, Suquet JP, Aubert R, De Gasquet P, Pequignot E . Metabolism of the mouse made obese by a high-fat diet Diabetes Metab 1975 1 2: 77–85.
Johnson PR, Hirsch J . Cellularity of adipose depots in six strains of genetically obese mice J Lipid Res 1972 13 1: 2–11.
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.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.ijo.0802161
Keywords
This article is cited by
-
Identification of genetic association between cardiorespiratory fitness and the trainability genes in childhood acute lymphoblastic leukemia survivors
BMC Cancer (2019)
-
Leptin gene polymorphism affects leptin level in childhood asthma
World Journal of Pediatrics (2018)
-
Leptin receptor gene (A/G) polymorphism rs1137101 and renal cell carcinoma
Molecular and Cellular Biochemistry (2018)
-
The Genetics of Physical Activity
Current Cardiology Reports (2017)
-
Leptin receptor gene polymorphisms and morbid obesity in Mexican patients
Hereditas (2016)