Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Paper
  • Published:

Interactions between physical activity and variants of the genes encoding uncoupling proteins −2 and −3 in relation to body weight changes during a 10-y follow-up

International Journal of Obesity volume 29, pages 93–99 (2005)Cite this article

Abstract

OBJECTIVE:

To examine interactions between physical activity and possibly functional variants of the genes encoding uncoupling proteins −2 and −3 in relation to body weight change. We hypothesize that physical inactivity acts synergistically with a 45 bp insertion variant in the 3′untranslated region (3′UTR) of the UCP2-gene and with a t-allele of codon −55 in the promoter of the UCP3-gene in relation to subsequent weight change.

DESIGN:

Population-based longitudinal study of cohorts of juvenile obese and nonobese men, who were identified at the mandatory draft board examination in Copenhagen and adjacent regions at a median age of 19 y in 1943–77 and later examined at general health surveys in 1981–83 and 1991–93. The juvenile obese cohort included 568 men who at the draft board had a BMI ≥31 kg/m2 and the cohort of controls included 717 randomly selected draftees.

MEASUREMENTS:

Height and weight were measured, and information about physical activity was collected from a self-administered questionnaire. The genotyping of the polymorphisms was performed using RFLP techniques. The main outcome measure was change in BMI during the 10-y follow-up period. Additional outcome measures were obesity, waist circumference and body fat mass index measured at follow-up.

RESULTS:

Physical activity, the 3′UTR insertion polymorphism and the −55 c/t polymorphism were not consistently associated with changes in BMI, and there were no evidence for interactions between the UCP-variants and physical activity in relation to changes in BMI. No evidence for interaction between the UCP-variants and physical activity was found in relation to the additional obesity measures.

CONCLUSION:

This study does not support that interactions between physical activity and variants in the UCP2- or UCP3-gene are major determinants of subsequent weight changes in Danish Caucasian men.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Maes HHM, Neale MC, Eaves LJ . Genetic and environmental factors in relative body weight and human adiposity. Behav Genet 1997; 27: 325–351.

    Article  CAS  Google Scholar 

  2. French SA, Story M, Jeffery RW . Environmental influences on eating and physical activity. Annu Rev Public Health 2001; 22: 309–335.

    Article  CAS  Google Scholar 

  3. Sørensen TIA, Echwald SM . Obesity genes. Identifying single genes involved in polygenic inheritance is not easy. BMJ 2001; 322: 631–632.

    Article  Google Scholar 

  4. Heitmann BL, Kaprio J, Harris JR, Rissanen A, Korkeila M, Koskenvuo M . Are genetic determinants of weight gain modified by leisure-time physical activity? A prospective study of Finnish twins. Am J Clin Nutr 1997; 66: 672–678.

    Article  CAS  Google Scholar 

  5. Verdich C, Clement K, Sørensen TIA . Nutrient–gene interactions in the control of obesity. In: Remacle C, Reusens B (eds) Functional Foods, Ageing and Degenerative Disease. Chapter 10, Woodhead Publishing; 2004. pp 223–260.

    Chapter  Google Scholar 

  6. Fogelholm M, Kukkonen-Harjula K . Does physical activity prevent weight gain—a systematic review. Obes Rev 2000; 24: 131–143.

    Google Scholar 

  7. Saris WHM, Blair SN, van Baak MA, Eaton SB, Davies PSW, Di Pietro L, Fogelholm M, Rissanen A, Schoeller D, Swinburn B, Tremblay A, Westerterp KR, Wyatt H . How much physical activity is enough to prevent unhealthy weight gain? Outcome of the IASO 1st Stick Conference and Consensus Statement. Obes Rev 2003; 4: 101–114.

    Article  CAS  Google Scholar 

  8. Petersen L, Schnohr P, Sørensen TIA . Longitudinal study of the relation between physical activity and obesity in adults. Int J Obes Relat Metab Disord 2004; 28: 105–112.

    Article  CAS  Google Scholar 

  9. Bak H, Petersen L, Sørensen TIA . Physical activity in relation to development and maintenance of obesity in men with and without juvenile onset obesity. Int J Obes Relat Metab Disord 2004; 28: 99–104.

    Article  CAS  Google Scholar 

  10. Krauss S, Zhang CY, Lowell BB . A significant portion of mitochondrial proton leak in intact thymocytes depends on expression of UCP2. Proc Natl Acad Sci USA 2002; 8: 118–122.

    Article  Google Scholar 

  11. Dalgaard LT, Pedersen O . Uncoupling proteins: functional characteristics and role in the pathogenesis of obesity and Type II diabetes. Diabetologia 2001; 44: 946–965.

    Article  CAS  Google Scholar 

  12. Urhammer SA, Dalgaard LT, Sørensen TIA, Tybjærg_Hansen A, Echwald SM, Andersen T, Clausen JO, Pedersen O . Organisation of the coding exons and mutational screening of the uncoupling protein 3 gene in subjects with juvenile-onset obesity. Diabetologia 1998; 41: 241–244.

    Article  CAS  Google Scholar 

  13. Dalgaard LT, Sørensen TIA, Andersen T, Hansen T, Pedersen O . An untranslated insertion variant in the uncoupling protein 2 gene is not related to BMI and changes in body weight during a 26-year follow-up in Danish Caucasian men. Diabetologia 1999; 42: 1413–1416.

    Article  CAS  Google Scholar 

  14. Walder K, Norman RA, Hanson RL, Schrauwen P, Neverova M, Jenkinson CP, Easlick J, Warden CH, Pecqueur C, Raimbault S, Richquier D, Harper M, Silver K, Shuldiner AR, Solanes G, Lowell BB, Chung WK, Leibel RL, Pratley R, Ravussin E . Association between uncoupling protein polymorphism (UCP2–UCP3) and energy metabolism/obesity in Pima Indians. Hum mol Genet 1998; 7: 1431–1435.

    Article  CAS  Google Scholar 

  15. Cassel PG, Neverova M, Jammohamed S, Uwakwe N, Qureshi A, McCarthy MI, Saker PJ, Albon L, Kopelman P, Noonan K, Easlick J, Ramachandran A, Snehalatha C, Pecqueur C, Ricquier D, Warden C, Hitman GA . An uncoupling protein 2 gene variant is associated with a raised BMI but not type II diabetes. Diabetologia 1999; 42: 688–692.

    Article  Google Scholar 

  16. Otabe S, Clement K, Rich N, Warden C, Pecqueur C, Neverova M, Raimbault S, Guy-Grand B, Basdevant A, Ricquier D, Froguel P, Vasseur F . Mutation screening of the human UCP2 gene in normoglycemic and NIDDM morbidly obese patients: lack of association between new UCP2 polymorphisms and obesity in French Caucasians. Diabetes 1998; 47: 840–842.

    Article  CAS  Google Scholar 

  17. Esterbauer H, Schneitler C, Oberkofler H, Ebenbichler C, Paulweber B, Sandhofer F, Ladurner G, Hell E, Strosberg AD, Patsch JR, Krempler F, Patsch W . A common polymorphism in the promoter of UCP2 is associated with decreased risk of obesity in middle-aged humans. Nat Genet 2001; 28: 178–183.

    Article  CAS  Google Scholar 

  18. Halsall DJ, Luan J, Saker P, Huxtable S, Farooqi IS, Keogh J, Wareham NJ, O’Rahilly S . Uncoupling protein 3 genetic variants in human obesity: The c-55t promoter polymorphism is negatively correlated with BMI in a UK Caucasian population. Int J Obes Relat Metab Disord 2001; 25: 472–477.

    Article  CAS  Google Scholar 

  19. Otabe S, Clement K, Dina C, Pelloux V, Guy-Grand B, Froguel P, Vasseur . A genetic variation in the 5′ flanking region of the UCP3 gene is associated with BMI in humans in interaction with physical activity. Diabetologia 2000; 43: 245–249.

    Article  CAS  Google Scholar 

  20. Schrauwen P, Xia J, Walder K, Snitker S, Ravussin E . A novel polymorphism in the proximal UCP3 promoter region: effect on skeletal muscle UCP3 mRNA expression and obesity in male non-diabetic Pima Indians. Int J Obes Relat Metab Disord 1999; 23: 1242–1245.

    Article  CAS  Google Scholar 

  21. Meirhaeghe A, Amouyel P, Helbecque N, Cottel D, Otabe S, Froquel P, Vasseur F . An uncoupling protein 3 gene polymorphism associated with a lower risk of developing Type II diabetes and with atherogenic lipid profile in a French cohort. Diabetologia 2000; 43: 1424–1428.

    Article  CAS  Google Scholar 

  22. Dalgaard LT, Sørensen TIA, Drivsholm T, Borch-Johnsen K, Andersen T, Hansen T, Pedersen O . A prevalent polymorphism in the promoter of the UCP3 gene and its relationship to BMI and long term body weight change in the Danish population. J Clin Endocrinol Metab 2001; 86: 1398–1402.

    CAS  PubMed  Google Scholar 

  23. Schrauwen P, Troost FJ, Xia J, Ravussin E, Saris WHM . Skeletal muscle UCP2 and UCP3 expression in trained and untrained male subjects. Int J Obes Relat Metab Disord 1999; 23: 966–972.

    Article  CAS  Google Scholar 

  24. Buemann B, Schierning B, Toubro S, Bibby BM, Sørensen TIA, Dalgaard L, Pedersen O, Astrup A . The association between the val/ala-55 polymorphism of the uncoupling protein 2 gene and exercise efficiency. Int J Obes Relat Metab Disord 2001; 25: 467–471.

    Article  CAS  Google Scholar 

  25. Sonne-Holm S, Sørensen TIA, Jensen G, Schnohr P . Independent effects of weight change and attained body weight on prevalence of arterial hypertension in obese and non-obese men. BMJ 1989; 299: 767–799.

    Article  CAS  Google Scholar 

  26. Heitmann BL . Evaluation of body fat estimated from BMI, skinfolds and impedance. A comparative study. Eur J Clin Nutr 1990; 44: 831–837.

    CAS  Google Scholar 

  27. Saltin B, Grimby G . Physiological analysis of middle-aged and old former athletes. Comparison with still active athletes of same ages. Circulation 1968; 38: 1104–1115.

    Article  CAS  Google Scholar 

  28. Saltin B . Physiological effects of physical conditioning. In: Hansen AT, Schnohr P, Rose G (eds) Ischaemic Heart Disease. The Strategy of Postponement. Year Book Medical Publishers: Chicago and FADL's forlag: Copenhagen; 1977. pp 104–115.

    Google Scholar 

  29. Andersen LB, Schnohr P, Schroll M, Hein HO . All-cause mortality associated with physical activity during leisure time, work, sports, and cycling to work. Arch Intern Med 2000; 160: 1621–1628.

    Article  CAS  Google Scholar 

  30. Hippe M, Vestbo J, Hein HO, Borch-Johnsen K, Jensen G, Sørensen TIA . Familial predisposition and susceptibility to the effect of other risk factors for myocardial infarction. J Epidemiol Commun Health 1999; 53: 269–276.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The Danish Medical Research Council, The Danish Heart Foundation and The Danish National Research Foundation supported the study. We also thank the staff of the Copenhagen City Heart Study for their invaluable assistance in the two examinations.

Author information

Authors and Affiliations

  1. Danish Epidemiology Science Centre at the Institute of Preventive Medicine, Copenhagen University Hospital, Copenhagen, Denmark

    T Berentzen, L Petersen & T I A Sørensen

  2. Steno Diabetes Center, Gentofte, Denmark

    L T Dalgaard & O Pedersen

  3. Biochemistry Laboratory A, Department of Medical Biochemistry and Genetics, University of Copenhagen, Denmark

    L T Dalgaard

  4. Copenhagen City Heart Study, Copenhagen University Hospital, Denmark

    T I A Sørensen

Authors
  1. T Berentzen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. L T Dalgaard
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. L Petersen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. O Pedersen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. T I A Sørensen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to T I A Sørensen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Berentzen, T., Dalgaard, L., Petersen, L. et al. Interactions between physical activity and variants of the genes encoding uncoupling proteins −2 and −3 in relation to body weight changes during a 10-y follow-up. Int J Obes 29, 93–99 (2005). https://doi.org/10.1038/sj.ijo.0802841

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ijo.0802841

Keywords

This article is cited by

Search

Advanced search

Quick links