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Programming effects of FTO in the development of obesity

Authors

  • S. Sebert,

    Corresponding author
    1. Faculty of Medicine, Institute of Health Sciences, Centre For Life-Course Epidemiology, University of Oulu, Oulu, Finland
    2. Biocenter Oulu, University of Oulu, Oulu, Finland
    • Correspondence: Dr. S. Sebert,

      Institute of Health Sciences,

      Centre For Life Course Epidemiology,

      Faculty of Medicine, University of Oulu,

      Aapistie 5B, 90014, Oulu, Finland.

      E-mail: sylvain.sebert@oulu.fi

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  • T. Salonurmi,

    1. Biocenter Oulu, University of Oulu, Oulu, Finland
    2. Institute of Clinical Medicine, Department of Internal Medicine, and Medical Research Centre, University of Oulu, Oulu, Finland
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  • S. Keinänen-Kiukaanniemi,

    1. Faculty of Medicine, Institute of Health Sciences, Centre For Life-Course Epidemiology, University of Oulu, Oulu, Finland
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  • M. Savolainen,

    1. Biocenter Oulu, University of Oulu, Oulu, Finland
    2. Institute of Clinical Medicine, Department of Internal Medicine, and Medical Research Centre, University of Oulu, Oulu, Finland
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  • K.-H. Herzig,

    1. Biocenter Oulu, University of Oulu, Oulu, Finland
    2. Institute of Biomedicine, Department of Physiology, University of Oulu, Oulu, Finland
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  • M. E. Symonds,

    1. Early Life Nutrition Research Unit, Academic Division of Child Health, Obstetrics & Gynaecology, School of Medicine, Queen's Medical Centre, University Hospital, The University of Nottingham, Nottingham, UK
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  • M.-R. Järvelin

    1. Faculty of Medicine, Institute of Health Sciences, Centre For Life-Course Epidemiology, University of Oulu, Oulu, Finland
    2. Biocenter Oulu, University of Oulu, Oulu, Finland
    3. Department of Epidemiology and Biostatistics, MRC Health Protection Agency (HPA) Centre for Environment and Health, School of Public Health, Imperial College, London, UK
    4. Unit of Primary Care, Oulu University Hospital, Oulu, Finland
    5. Department of Children and Young People and Families, National Institute for Health and Welfare, Oulu, Finland
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Abstract

It is becoming increasingly recognized that early-life nutritional, metabolic and environmental factors can have a long-term impact on the early onset of obesity, type 2 diabetes and cardiovascular diseases. Numerous experimental and epidemiological observations support the concept that an individual's response to their adult lifestyle and nutritional environment depends not only on their genetic susceptibility but also on their previous early-life experiences. The current research challenge is to determine the primary pathways contributing to ‘non- or epi-genetic’ causes of excess adult weight gain and adiposity. Evidence from the fields of genetic epidemiology, life course modelling and diet-induced foetal programming all support a role for the FTO gene in this complex biological interaction. It may provide a missing link in the developmental regulation of energy metabolism. Our review therefore considers the role of the FTO gene in the early-life determination of body weight, body composition and energy balance. We will summarize current knowledge on FTO biology combining human genetic epidemiology, molecular models and findings from animal studies. Notably, we will focus on the role of FTO in energy balance in humans, the importance of FTO polymorphisms in childhood growth and the impact of foetal nutrition. Ultimately, we propose a new hypothesis for future research designed to understand the role of FTO in setting gene expression in metabolically active tissues.

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