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.

  • Original Article
  • Published:

Association between fat intake, physical activity and mortality depending on genetic variation in FTO

International Journal of Obesity volume 35, pages 1041–1049 (2011)Cite this article

Subjects

Abstract

Objective:

We wanted to explore if FTO genotype interacts with fat intake, or leisure-time physical activity, on fat mass, lean mass and mortality.

Subjects and methods:

Among 22 799 individuals (44–74 years) in the population-based Malmö diet and cancer cohort that were genotyped for rs9939609 in FTO and had information on dietary intake (from a modified diet history method) and no history of diabetes, cancer or cardiovascular disease, 2255 deaths (including 1100 cancer and 674 cardiovascular deaths) occurred during 12.0 years of follow-up. Leisure-time physical activity was determined from a list of 17 different physical activities in a questionnaire. Body composition was measured using bioelectric impedance method.

Results:

FTO genotype associated strongly with both fat mass and lean mass (Ptrend<1 × 10−16 for both) but we found only significant interactions with fat intake, or physical activity, on fat mass (Pinteraction=0.01 and 0.004). No significant interaction between FTO genotype and fat intake (Pinteraction=0.72), or leisure-time physical activity (Pinteraction=0.07), on total mortality were observed. However, we observed a significant interaction between leisure-time physical activity and FTO genotype on cardiovascular mortality (Pinteraction=0.03). The highest vs lowest quintile of physical activity was associated with 46% (95% confidence interval, 17–64%) reduced cardiovascular mortality among TT-carriers (Ptrend=0.004), and 11% reduced cardiovascular mortality among A-allele carriers (Ptrend=0.68).

Conclusion:

Our results indicate that FTO genotype associates with both fat mass and lean mass, but the level of fat intake and physical activity only modify the association with fat mass. In addition, FTO genotype may modify the association between physical activity and cardiovascular mortality.

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

Figure 1

Similar content being viewed by others

References

  1. Cecil JE, Tavendale R, Watt P, Hetherington MM, Palmer CN . An obesity-associated FTO gene variant and increased energy intake in children. N Engl J Med 2008; 359: 2558–2566.

    Article  CAS  PubMed  Google Scholar 

  2. Timpson NJ, Emmett PM, Frayling TM, Rogers I, Hattersley AT, McCarthy MI et al. The fat mass- and obesity-associated locus and dietary intake in children. Am J Clin Nutr 2008; 88: 971–978.

    Article  CAS  PubMed  Google Scholar 

  3. Wardle J, Llewellyn C, Sanderson S, Plomin R . The FTO gene and measured food intake in children. Int J Obes (2005) 2009; 33: 42–45.

    Article  CAS  Google Scholar 

  4. Wardle J, Carnell S, Haworth CM, Farooqi IS, O’ahilly S, Plomin R . Obesity associated genetic variation in FTO is associated with diminished satiety. J Clin Endocrinol Metab 2008; 93: 3640–3643.

    Article  CAS  PubMed  Google Scholar 

  5. Speakman JR, Rance KA, Johnstone AM . Polymorphisms of the FTO gene are associated with variation in energy intake, but not energy expenditure. Obesity (Silver Spring) 2008; 16: 1961–1965.

    Article  CAS  Google Scholar 

  6. Fischer J, Koch L, Emmerling C, Vierkotten J, Peters T, Bruning JC et al. Inactivation of the Fto gene protects from obesity. Nature 2009; 458: 894–898.

    Article  CAS  PubMed  Google Scholar 

  7. Haupt A, Thamer C, Staiger H, Tschritter O, Kirchhoff K, Machicao F et al. Variation in the FTO gene influences food intake BUT not energy expenditure. Exp Clin Endocrinol Diabetes 2009; 117: 194–197.

    Article  CAS  PubMed  Google Scholar 

  8. Berentzen T, Kring SI, Holst C, Zimmermann E, Jess T, Hansen T et al. Lack of association of fatness-related FTO gene variants with energy expenditure or physical activity. J Clin Endocrinol Metab 2008; 93: 2904–2908.

    Article  CAS  PubMed  Google Scholar 

  9. Goossens GH, Petersen L, Blaak EE, Hul G, Arner P, Astrup A et al. Several obesity- and nutrient-related gene polymorphisms but not FTO and UCP variants modulate postabsorptive resting energy expenditure and fat-induced thermogenesis in obese individuals: the NUGENOB Study. Int J Obes (2005) 2009; 33: 669–679.

    Article  CAS  Google Scholar 

  10. Zimmermann E, Kring SI, Berentzen TL, Holst C, Pers TH, Hansen T et al. Fatness-associated FTO gene variant increases mortality independent of fatness—in cohorts of Danish men. PLoS One 2009; 4: e4428.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Sonestedt E, Roos C, Gullberg B, Ericson U, Wirfalt E, Orho-Melander M . Fat and carbohydrate intake modify the association between genetic variation in the FTO genotype and obesity. Am J Clin Nutr 2009; 90: 1418–1425.

    Article  CAS  PubMed  Google Scholar 

  12. Andreasen CH, Stender-Petersen KL, Mogensen MS, Torekov SS, Wegner L, Andersen G et al. Low physical activity accentuates the effect of the FTO rs9939609 polymorphism on body fat accumulation. Diabetes 2008; 57: 95–101.

    Article  CAS  PubMed  Google Scholar 

  13. Rampersaud E, Mitchell BD, Pollin TI, Fu M, Shen H, O’Connell JR et al. Physical activity and the association of common FTO gene variants with body mass index and obesity. Arch Intern Med 2008; 168: 1791–1797.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Cauchi S, Stutzmann F, Cavalcanti-Proenca C, Durand E, Pouta A, Hartikainen AL et al. Combined effects of MC4R and FTO common genetic variants on obesity in European general populations. J Mol Med 2009; 87: 537–546.

    Article  CAS  PubMed  Google Scholar 

  15. Ruiz JR, Labayen I, Ortega FB, Legry V, Moreno LA, Dallongeville J et al. Attenuation of the effect of the FTO rs9939609 polymorphism on total and central body fat by physical activity in adolescents: the HELENA study. Arch Pediatr Adolesc Med 2010; 164: 328–333.

    Article  PubMed  Google Scholar 

  16. Hedblad B, Nilsson P, Engstrom G, Berglund G, Janzon L . Insulin resistance in non-diabetic subjects is associated with increased incidence of myocardial infarction and death. Diabet Med 2002; 19: 470–475.

    Article  CAS  PubMed  Google Scholar 

  17. Callmer E, Riboli E, Saracci R, Akesson B, Lindgarde F . Dietary assessment methods evaluated in the Malmo food study. J Intern Med 1993; 233: 53–57.

    Article  CAS  PubMed  Google Scholar 

  18. Wirfalt E, Mattisson I, Johansson U, Gullberg B, Wallstrom P, Berglund G . A methodological report from the Malmo diet and cancer study: development and evaluation of altered routines in dietary data processing. Nutr J 2002; 1: 3.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Riboli E, Elmstahl S, Saracci R, Gullberg B, Lindgarde F . The Malmo Food Study: validity of two dietary assessment methods for measuring nutrient intake. Int J Epidemiol 1997; 26 (Suppl 1): S161–S173.

    Article  PubMed  Google Scholar 

  20. Taylor HL, Jacobs Jr DR, Schucker B, Knudsen J, Leon AS, Debacker G . A questionnaire for the assessment of leisure time physical activities. J Chronic Dis 1978; 31: 741–755.

    Article  CAS  PubMed  Google Scholar 

  21. Li C, Aronsson CA, Hedblad B, Gullberg B, Wirfalt E, Berglund G . Ability of physical activity measurements to assess health-related risks. Eur J Clin Nutr 2009; 63: 1448–1451.

    Article  CAS  PubMed  Google Scholar 

  22. Calling S, Hedblad B, Engstrom G, Berglund G, Janzon L . Effects of body fatness and physical activity on cardiovascular risk: risk prediction using the bioelectrical impedance method. Scand J Public Health 2006; 34: 568–575.

    Article  PubMed  Google Scholar 

  23. Sonestedt E, Gullberg B, Wirfalt E . Both food habit change in the past and obesity status may influence the association between dietary factors and postmenopausal breast cancer. Public Health Nutr 2007; 10: 769–779.

    Article  PubMed  Google Scholar 

  24. Sonestedt E, Wirfalt E, Gullberg B, Berglund G . Past food habit change is related to obesity, lifestyle and socio-economic factors in the Malmo diet and cancer cohort. Public Health Nutr 2005; 8: 876–885.

    Article  PubMed  Google Scholar 

  25. Mattisson I, Wirfalt E, Aronsson CA, Wallstrom P, Sonestedt E, Gullberg B et al. Misreporting of energy: prevalence, characteristics of misreporters and influence on observed risk estimates in the Malmo diet and cancer cohort. Br J Nutr 2005; 94: 832–842.

    Article  CAS  PubMed  Google Scholar 

  26. WHO. Energy and protein requirements: report of a Joint FAO/WHO/UNU Expert Consultation. World Health Organization: Geneva, 1985, 206pp.

  27. Black AE . Critical evaluation of energy intake using the Goldberg cut-off for energy intake: basal metabolic rate. A practical guide to its calculation, use and limitations. Int J Obes Relat Metab Disord 2000; 24: 1119–1130.

    Article  CAS  PubMed  Google Scholar 

  28. Linseisen J, Welch AA, Ocke M, Amiano P, Agnoli C, Ferrari P et al. Dietary fat intake in the European prospective investigation into cancer and nutrition: results from the 24-h dietary recalls. Eur J Clin Nutr 2009; 63 (Suppl 4): S61–S80.

    Article  CAS  PubMed  Google Scholar 

  29. Frayling TM, Timpson NJ, Weedon MN, Zeggini E, Freathy RM, Lindgren CM et al. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 2007; 316: 889–894.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Jess T, Zimmermann E, Kring SI, Berentzen T, Holst C, Toubro S et al. Impact on weight dynamics and general growth of the common FTO rs9939609: a longitudinal Danish cohort study. Int J obes (2005) 2008; 32: 1388–1394.

    Article  CAS  Google Scholar 

  31. Vimaleswaran KS, Li S, Zhao JH, Luan J, Bingham SA, Khaw KT et al. Physical activity attenuates the body mass index-increasing influence of genetic variation in the FTO gene. Am J Clin Nutr 2009; 90: 1418–1425.

    Article  Google Scholar 

Download references

Acknowledgements

This study is supported by the Lund University Diabetes Center (LUDC), the Swedish Medical Research Council, equipment grant from the Knut and Alice Wallenberg Foundation, the Swedish Heart and Lung Foundation, the Region Skåne, the Malmö University Hospital, the Albert Påhlsson Research Foundation and the Crafoord foundation.

Author information

Authors and Affiliations

  1. Department of Clinical Sciences in Malmö, Diabetes and Cardiovascular disease—genetic epidemiology, Lund University, Malmö, Sweden

    E Sonestedt, U Ericson & M Orho-Melander

  2. Department of Clinical Sciences in Malmö, Nutrition Epidemiology, Lund University, Malmö, Sweden

    B Gullberg & E Wirfält

  3. Department of Clinical Sciences in Malmö, Cardiovascular Epidemiology, Lund University, Malmö, Sweden

    B Hedblad

Authors
  1. E Sonestedt
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. B Gullberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. U Ericson
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. E Wirfält
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. B Hedblad
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M Orho-Melander
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to E Sonestedt.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sonestedt, E., Gullberg, B., Ericson, U. et al. Association between fat intake, physical activity and mortality depending on genetic variation in FTO. Int J Obes 35, 1041–1049 (2011). https://doi.org/10.1038/ijo.2010.263

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ijo.2010.263

Keywords

This article is cited by

Search

Advanced search

Quick links