Programming effects of FTO in the development of obesity

AbstractIt is becoming increasingly recognized that early-life nutritional, metabolicand environmental factors can have a long-term impact on the early onsetof obesity, type 2 diabetes and cardiovascular diseases. Numerous experi-mental and epidemiological observations support the concept that an indi-vidual’s response to their adult lifestyle and nutritional environmentdepends not only on their genetic susceptibility but also on their previousearly-life experiences. The current research challenge is to determine theprimary pathways contributing to ‘non- or epi-genetic’ causes of excessadult weight gain and adiposity. Evidence from the fields of genetic epide-miology, life course modelling and diet-induced foetal programming allsupport a role for the FTO gene in this complex biological interaction. Itmay provide a missing link in the developmental regulation of energymetabolism. Our review therefore considers the role of the FTO gene inthe early-life determination of body weight, body composition and energybalance. We will summarize current knowledge on FTO biology combin-ing human genetic epidemiology, molecular models and findings from ani-mal studies. Notably, we will focus on the role of FTO in energy balancein humans, the importance of FTO polymorphisms in childhood growthand the impact of foetal nutrition. Ultimately, we propose a new hypothe-sis for future research designed to understand the role of FTO in settinggene expression in metabolically active tissues.Keywords animal models, early life, foetal programming, FTO, geneticepidemiology, obesity.