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Beta-2 adrenergic receptor variants are associated with subcutaneous fat accumulation in response to long-term overfeeding

International Journal of Obesity volume 25, pages 1604–1608 (2001)Cite this article

Abstract

OBJECTIVE: The effects of alpha-2A (A2A)-, beta-2 (B2)- and beta-3 (B3)-adrenergic receptor (ADR) gene polymorphisms on adiposity, fat distribution and plasma insulin and leptin changes in response to long-term overfeeding were explored.

METHODS: Twenty four men (mean (±s.d.) age 21±2 y) who constituted 12 pairs of identical twins ate a 4.2 MJ/day energy surplus, 6 days a week, for a period of 100 days. Total body fat was assessed by hydrodensitometry and total subcutaneous fat by the sum of eight skinfolds. Abdominal fat areas were measured by computerized tomography (CT). Plasma glucose and insulin during fasting and in response to an oral glucose tolerance test (OGTT) were assayed. The insulin and glucose areas were computed using the trapezoidal method. Plasma leptin was measured with an enzyme-linked immunosorbent assay. The ADR polymorphisms were identified by PCR or Southern blot technique.

RESULTS: The ADRB2 Gln27Gln genotype (n=10) was associated with a larger gain (percentage change) in weight (P<0.001) and total subcutaneous (P<0.005) fat than the Glu27Glu/Gln27Glu genotype (n=14). In addition, overfeeding induced greater increases in the insulin areas under the curve during the OGTT and the fasting plasma level of leptin (P<0.01 and <0.03, respectively) among Gln27Gln than in the Glu27Glu/Gln27Glu subjects. The body composition and metabolic changes among the ADRB2 BanI 3.7/3.4 kb subjects (n=10) were similar to those of Gln27Gln subjects. ADRA2A DraI (n=4) 6.3/6.3 kb subjects experienced a decrease (−8%) while 6.7/6.3 kb subjects (n=20) registered an increase (+10%; P=0.017) of OGTT glucose area after the 100-day caloric surplus. The four carriers of the ADRB3 variant (Trp64Arg) experienced the same magnitude of changes as the 20 homozygotes for the Trp allele. In general, comparisons based on the 24 subjects considered as unrelated men and the mean values for each of the 12 pairs yielded similar results.

CONCLUSION: The ADRB2 Gln27Gln subjects gained more weight and total subcutaneous fatness and also experienced a greater increase in insulin resistance than Glu27Glu/Gln27Glu subjects with exposure to long-term overfeeding. Similar differences were observed between carriers and non-carriers of the ADRB2 3.7/3.4 kb BanI variant. Genetic variation at the ADRB2 locus could thus be one of the factors responsible for the large inter-individual differences observed in the response to long-term alterations in energy balance and should be further investigated.

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References

  1. Lafontan M . Differential recruitment and differential regulation by physiological amines of fat cell β1, β2, and β3-adrenergic receptors expressed in native fat cells and in transfected cell lines Cell Signal 1994 6: 363–392.

    Article  CAS  Google Scholar 

  2. Galitzky J, Mauriége P, Berlan M, Lafontan M . Human fat cell alpha-2 adrenoceptors. I. Functional exploration and pharmacological definition with selected alpha-2 agonists and antagonists J Pharmac Exp Ther 1989 249: 583–591.

    CAS  Google Scholar 

  3. Large V, Hellstrom L, Reynisdottir S, Lonnqvist F, Eriksson P, Lannfelt L, Arner P . Human beta-2 adrenoceptor gene polymorphisms are highly frequent in obesity and associate with altered adipocyte beta-2 adrenoceptor function J Clin Invest 1997 100: 3005–3013.

    Article  CAS  Google Scholar 

  4. Hellstrom L, Large V, Reynisdottir S, Wahrenberg H, Arner P . The different effects of a Gln27Glu β2-adrenoceptor gene polymorphism on obesity in males and females J Intern Med 1999 245: 253–259.

    Article  CAS  Google Scholar 

  5. Ishiyama-Shigemoto S, Yamada K, Yuan X, Ichikawa F, Nonaka K . Association of polymorphisms in the β2-adrenergic receptor gene with obesity, hypertriglyceridaemia, and diabetes mellitus Diabetologia 1999 42: 98–101.

    Article  CAS  Google Scholar 

  6. Oppert JM, Tourville J, Chagnon M, Mauriége P, Dionne FT, Pérusse L, Bouchard C . DNA polymorphisms in the α2- and β2-adrenoceptor genes and regional fat distribution in humans: association and linkage studies Obes Res 1995 3: 249–255.

    Article  CAS  Google Scholar 

  7. Oberkofler H, Esterbauer H, Hell E, Krempler F, Patsch W . The Gln27Glu polymorphism in the beta2-adrenergic receptor gene is not associated with morbid obesity in Austrian women Int J Obes Relat Metab Disord 2000 24: 388–390.

    Article  CAS  Google Scholar 

  8. Kortner B, Wolf A, Wendt D, Beisiegel U, Evans D . Lack of association between a human beta-2 adrenoceptor gene polymorphism (gln27glu) and morbid obesity Int J Obes Relat Metab Disord 1999 23: 1099–1100.

    Article  CAS  Google Scholar 

  9. Echwald SM, Sorensen TI, Tybjaerg-Hansen A, Andersen T, Pedersen O . Gln27Glu variant of the human beta2-adrenoreceptor gene is not associated with early-onset obesity in Danish men Diabetes 1998 47: 1657–1658.

    Article  CAS  Google Scholar 

  10. Allison DB, Heo M, Faith MS, Pietrobelli A . Meta-analysis of the association of the Trp64Arg polymorphism in the beta3 adrenergic receptor with body mass index Int J Obes Relat Metab Disord 1998 22: 559–566.

    Article  CAS  Google Scholar 

  11. Bouchard C, Tremblay A, Després J-P, Nadeau A, Lupien PJ, Theriault G, Dussault J, Moorjani S, Pinault S, Fournier G . The response to long-term overfeeding in identical twins New Engl J Med 1990 322: 1477–1482.

    Article  CAS  Google Scholar 

  12. Lohman T, Roche AF, Martorell R (eds) . Anthropometric standardization reference manual Human Kinetics: Champaign, IL 1988

    Google Scholar 

  13. Bouchard C, Tremblay A, Després J-P, Nadeau A, Lupien PJ, Moorjani S, Theriault G, Kim SY . Overfeeding in identical twins: 5-year postoverfeeding results Metabolism 1996 45: 1042–1050.

    Article  CAS  Google Scholar 

  14. Wisse BE, Campfield LA, Marliss SB, Morais JA, Tenenbaum R, Gougeon R . Effect of prolonged moderate and severe energy restriction and refeeding on plasma leptin concentrations in obese women Am J Clin Nutr 1999 70: 321–330.

    Article  CAS  Google Scholar 

  15. Ukkola O, Rankinen T, Weisnagel SJ, Sun G, Pérusse L, Chagnon YC, Després J-P, Bouchard C . Interactions among the α2-, β2- and β3-adrenergic receptor genes and obesity-related phenotypes in the Québec Family Study Metabolism 2000 49: 1063–1070.

    Article  CAS  Google Scholar 

  16. Meirhaeghe A, Helbecque N, Cottel D, Amouyel P . Impact of polymorphisms of the human beta2-adrenoceptor gene on obesity in a French population Int J Obes Relat Metab Disord 2000 24: 382–387.

    Article  CAS  Google Scholar 

  17. Ohe M, Munakata M, Hizawa N, Itoh A, Doi I, Yamaguchi E, Homma Y, Kawakami Y . Beta 2 adrenergic receptor gene restriction fragment length polymorphism and bronchial asthma Thorax 1995 50: 353–359.

    Article  CAS  Google Scholar 

  18. Dewar JC, Wheatley AP, Venn A, Morrison JF, Britton J, Hall IP . Beta2-adrenoceptor polymorphisms are in linkage disequilibrium, but are not associated with asthma in an adult population Clin Exp Allergy 1998 28: 442–448.

    Article  CAS  Google Scholar 

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Acknowledgements

We are indebted to Jacques Bouillon, Suzie Hamel, Brigitte Zément, Maryse Lebrun, Martine Marcotte, Monique Chagnon, Josée Lapointe, Henri Bessette, Gilles Bouchard and Serge Carbonneau for their contributions to this study. Gratitude is expressed to Dr A Nadeau and the staff of the Diabetes Research Unit for the glucose and insulin assays. We thank Dr L Arthur Campfield for the leptin assay. Special thanks go to Guy Fournier and Dr Germain Thériault for their role in the management of the study and to Claude Leblanc for his statistical support. Supported in part by a grant (DK 34624) from the National Institutes of Health and the Finnish Heart Foundation. C Bouchard is supported in part by the George A Bray Chair in Nutrition.

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Authors and Affiliations

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

    O Ukkola & C Bouchard

  2. Department of Internal Medicine and Biocenter Oulu, University of Oulu, Oulu, Finland

    O Ukkola

  3. Division of Kinesiology, Physical Activity Sciences Laboratory, Laval University, Ste-Foy, Québec, Canada

    A Tremblay

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  1. O Ukkola
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Correspondence to C Bouchard.

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Ukkola, O., Tremblay, A. & Bouchard, C. Beta-2 adrenergic receptor variants are associated with subcutaneous fat accumulation in response to long-term overfeeding. Int J Obes 25, 1604–1608 (2001). https://doi.org/10.1038/sj.ijo.0801810

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