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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

International Journal of Obesity volume 33, pages 669–679 (2009)Cite this article

Abstract

Background:

Part of the heterogeneity of the obesity phenotype may originate from genetic differences between obese individuals that may influence energy expenditure (EE).

Objective:

To examine if common single-nucleotide polymorphisms (SNPs) in genes related to obesity-associated phenotypes are associated with postabsorptive resting energy expenditure (REE) and postprandial REE in obese individuals.

Design and methods:

Postabsorptive REE and 3-h postprandial REE (liquid test meal containing 95% fat, energy content 50% of estimated REE) were measured in 743 obese individuals from eight clinical centres in seven European countries. The analysis assessed the association of genotypes of 44 SNPs in 28 obesity-related candidate genes with postabsorptive REE and postprandial REE taking into consideration the influence of body composition, habitual physical activity, insulin sensitivity, circulating thermogenic hormones and metabolites.

Results:

After adjustment for fat-free mass (FFM), age, sex and research centre, SNPs in CART, GAD2, PCSK1, PPARG3, HSD11B1 and LIPC were significantly associated with postabsorptive REE. SNPs in GAD2, HSD11B1 and LIPC remained significantly associated with postabsorptive REE after further adjustment for fat mass (FM). SNPs in CART, PPARG2 and IGF2 were significantly associated with postprandial REE after similar adjustments. These associations with postprandial REE remained significant after further adjustment for FM. FTO, UCP2 and UCP3 variants were not associated with postabsorptive or postprandial REE.

Conclusions:

Several gene polymorphisms associated with obesity-related phenotypes but not FTO and UCP variants may be responsible for some of the inter-individual variability in postabsorptive REE and fat-induced thermogenesis unaccounted for by FFM, FM, age and sex. The association between FTO and obesity that has been reported earlier may not be mediated directly through modulation of EE in obese individuals.

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Acknowledgements

We acknowledge Claus Holst for his valuable contribution regarding the analytical strategy used in this study. This study was supported by the European Community (Contract no. QLK1-CT-2000-00618). The funding organization had no role in the preparation of the manuscript.

Author information

Author notes

  1. G H Goossens, L Petersen, E E Blaak, G Hul, P Arner, A Astrup, P Froguel, K Patel, O Pedersen, J Polak, J-M Oppert, J A Martinez, T I A Sørensen and W H M Saris: NUGENOB is the acronym of the project Nutrient-Gene Interactions in Human Obesity: Implications for Dietary Guidelines. www.nugenob.org

Authors and Affiliations

  1. Department of Human Biology, Nutrition and Toxicology Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands

    G H Goossens, E E Blaak, G Hul & W H M Saris

  2. National Centre for Register-based Research, University of Aarhus, Aarhus, Denmark

    L Petersen

  3. Department of Medicine, The Obesity Unit, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden

    P Arner

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

    A Astrup

  5. CNRS UPRES A 8090, Institut Biologie de Lille, Institut Pasteur de Lille, Lille, France

    P Froguel

  6. Queen's Medical Centre, School of Biomedical Sciences, University of Nottingham Medical School, Nottingham, UK

    K Patel

  7. Steno Diabetes Center, Copenhagen, Denmark

    O Pedersen

  8. Department of Sports Medicine, Third Faculty of Medicine, Centre of Preventive Medicine, Charles University, Praha, Czech Republic

    J Polak

  9. Department of Nutrition, Pitie Salpetriere Hospital, University Pierre-et-Marie Curie (Paris 6), Human Nutrition Research Centre Ile-de-France, Paris, France

    J-M Oppert

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

    J A Martinez

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

    T I A Sørensen

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Correspondence to G H Goossens.

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Goossens, G., Petersen, L., Blaak, E. 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 33, 669–679 (2009). https://doi.org/10.1038/ijo.2009.59

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