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  • Original Article
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Macronutrient-specific effect of FTO rs9939609 in response to a 10-week randomized hypo-energetic diet among obese Europeans

International Journal of Obesity volume 33, pages 1227–1234 (2009)Cite this article

Abstract

Background:

The A risk allele of rs9939609 of the fat mass- and obesity-associated gene (FTO) increases body fat mass.

Objective:

To examine whether FTO rs9939609 affects obese individuals' response to a high-fat, low-carbohydrate (CHO) (HF) or low-fat, high-CHO (LF), hypo-energetic diet and whether the effect of the FTO variant depends on dietary fat and CHO content.

Design:

In a 10-week, European, multi-centre dietary intervention study 771 obese women and men were randomized to either LF (20–25% of energy (%E) from fat, 60–65%E from CHO) or HF (40–45%E from fat, 40–45%E from CHO), hypo-energetic diet (measured resting metabolic rate multiplied by 1.3–600 kcal day−1). Body weight, fat mass (FM), fat-free mass (FFM), waist circumference (WC), resting energy expenditure (REE), fasting fat oxidation as % of REE (FatOx), insulin release (HOMA-β) and a surrogate measure of insulin resistance (HOMA-IR) were measured at baseline and after the intervention. In all, 764 individuals were genotyped for FTO rs9939609.

Results:

For A-allele carriers the drop-out rate was higher on HF than LF diet (in AT, P=0.002; in AT/AA combined, P=0.003). Among those individuals completing the intervention, we found no effect of FTO rs9939609 genotype on Δweight, ΔFM, ΔFFM, ΔWC or ΔFatOx. However, participants with TT had a smaller reduction in REE on LF than on HF diet (75 kcal/24 h; interaction: P=0.0055). These individuals also showed the greatest reduction in HOMA-β and HOMA-IR (interaction: P=0.0083 and P=0.047).

Conclusion:

The FTO rs9939609 may interact with the macronutrient composition in weight loss diets in various ways; carriers of the A allele on LF diet appear to have a lower risk for drop out, and TT individuals have a smaller decrease in REE and greater decrease in HOMA-β and HOMA-IR on LF than on HF diet.

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Acknowledgements

NUGENOB is the acronym of the project ‘Nutrient–Gene interactions in human obesity—implications for dietary guidelines’ supported by the European Community (Contract no. QLK1-CT-2000-00618), see the web-site www.nugenob.org. The study was supported by the European Community (Contract no. QLK1-CT-2000-00618).

Author information

Authors and Affiliations

  1. Institute of Preventive Medicine, Copenhagen University Hospital, Centre for Health and Society, Copenhagen, Denmark

    K Grau, C Holst & T I A Sørensen

  2. Center for Pharmacogenomics, The Panum Institute, University of Copenhagen, Copenhagen, Denmark

    K Grau

  3. Steno Diabetes Center, Copenhagen, Denmark

    T Hansen & O Pedersen

  4. Department of Human Nutrition, Faculty of Life Science, University of Copenhagen, Copenhagen, Denmark

    A Astrup

  5. Department of Human Biology, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, Maastricht, The Netherlands

    W H M Saris

  6. Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden

    P Arner

  7. Department of Medicine, Obesity Unit, Karolinska Institute, Karolinska University Hospital, Huddinge, Sweden

    S Rössner

  8. School of Biomedical Science, University of Nottingham Medical School, Queen's Medical Centre, Nottingham, UK,

    I Macdonald

  9. Department of Sport Medicine, Third Faculty of Medicine, Charles University in Prague, Prague, Czech Republic

    J Polak

  10. Department of Nutrition, Hôtel-Dieu Hospital (AP-HP); Human Nutrition Research Center Ile-de-France (CRNH-IdF),

    J-M Oppert

  11. Human Nutrition Research Center Ile-de-France (CRNH-IdF), Paris, France

    J-M Oppert

  12. Inserm; U858; F-31432 Toulouse, France,

    D Langin

  13. U858,

    D Langin

  14. Université de Toulouse; UPS; Institut de Médecine Moléculaire de Rangueil; IFR31, F-31432,

    D Langin

  15. UPS, Toulouse, France

    D Langin

  16. CHU de Toulouse; F-31432 Toulouse, France,

    D Langin

  17. F-31432 Toulouse, France,

    D Langin

  18. Department of Physiology and Nutrition, University of Navarra, Pamplona, Spain

    J A Martinez

  19. Hagedorn Research Institute, Copenhagen, Denmark

    O Pedersen

  20. Institute of Biomedicine, Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark

    O Pedersen

  21. Faculty of Health Science, University of Aarhus, Aarhus, Denmark

    O Pedersen

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Correspondence to K Grau.

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Grau, K., Hansen, T., Holst, C. et al. Macronutrient-specific effect of FTO rs9939609 in response to a 10-week randomized hypo-energetic diet among obese Europeans. Int J Obes 33, 1227–1234 (2009). https://doi.org/10.1038/ijo.2009.159

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