Physical activity attenuates the effect of the FTO genotype on obesity-related traits in European adults: Findings from the Food4Me study

Authors: CELIS-MORALES, CARLOS - Newcastle University; MARSAUX, CYRIL - Maastricht University; LIVINGSTONE, KATHERINE - Newcastle University; NAVAS-CARRETERO, SANTIAGO - University Of Navarra; SAN-CRISTOBAL, RODRIGO - University Of Navarra; O'DONOVAN, CLARE - University College Dublin; FORSTER, HANNAH - University College Dublin; WOOLHEAD, CLARA - University College Dublin; FALLAIZE, ROSALIND - University Of Reading; MACREADY, ANNA - University Of Reading; KOLOSSA, SILVIA - Technische Universitat Munchen; HALLMANN, JACQUELINE - Technische Universitat Munchen; TSIRIGOTI, LYDIA - Harokopio University Of Athens; LAMBRINOU, CHRISTINA - Harokopio University Of Athens; MOSCHONIS, GEORGE - Harokopio University Of Athens; GODLEWSKA, MAGDALENA - Instytut Zywnosci Zywienia; SURWILLO, AGNIESZKA - Instytut Zywnosci Zywienia; GRIMALDI, KEITH - Eurogenetica Ltd; BOUWMAN, JILDAU - Tno Quality Of Life; MANIOS, YANNIS - Harokopio University Of Athens; TRACZYK, IWONA - Instytut Zywnosci Zywienia; DREVON, CHRISTIAN - University Of Oslo; Parnell, Laurence; DANIEL, HANNELORE - Technische Universitat Munchen; GIBNEY, EILEEN - University College Dublin; BRENNAN, LORRAINE - University College Dublin; WALSH, MARIANNE - University College Dublin; GIBNEY, MIKE - University College Dublin; LOVEGROVE, JULIE - University Of Reading; MARTINEZ, J ALFREDO - University Of Navarra; SARIS, WIM - Maastricht University; MATHERS, JOHN - Newcastle University

Submitted to: International Journal of Obesity
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/19/2015
Publication Date: 2/27/2016
Citation: Celis-Morales, C., Marsaux, C.F., Livingstone, K.M., Navas-Carretero, S., San-Cristobal, R., O'Donovan, C.B., Forster, H., Woolhead, C., Fallaize, R., Macready, A.L., Kolossa, S., Hallmann, J., Tsirigoti, L., Lambrinou, C.P., Moschonis, G., Godlewska, M., Surwillo, A., Grimaldi, K., Bouwman, J., Manios, Y., Traczyk, I., Drevon, C.A., Parnell, L.D., Daniel, H., Gibney, E.R., Brennan, L., Walsh, M., Gibney, M., Lovegrove, J.A., Martinez, J., Saris, W.H., Mathers, J.C. 2016. Physical activity attenuates the effect of the FTO genotype on obesity-related traits in European adults: Findings from the Food4Me study. International Journal of Obesity. 24:962-969. doi: 10.1002/oby.21422.

Interpretive Summary: Genetic variation at the FTO (fat mass and obesity associated) gene is one of the strongest genetic determinants of human obesity yet discovered. Although many studies have shown that exercise can lessen the effects of the genetic factors in FTO that promote obesity, those studies used information that was less accurate because the level of exercise was reported by the study participants themselves. A large group of European and other nutrition and health researchers set out to examine the effects of exercise on obesity by measuring exercise very precisely with accelerometers, wearable devices that assess when a body is in motion and how strenuous the activity is. The results show that physical activity indeed lessens the effect of the obesity-promoting variation of the FTO gene. For example, the study found a larger waist circumference of over one inch in those individuals who are inactive and have the obesity-prone version of FTO compared to those who exercise moderately. These findings are important from a public health perspective because the genetics of FTO can be countered, in part, by adopting a physically active lifestyle.

Technical Abstract: Background. The FTO gene harbours the strongest known susceptibility locus for obesity. Studies of the interaction between genetic and environmental factors such as physical activity (PA) could contribute to the understanding of how lifestyle can modulate genetic susceptibility to obesity. In this study we examined whether the effect of FTO loci on obesity-related traits could be modified by PA levels in European adults. Methods. 1,280 individuals from the Food4Me randomised controlled trial (RCT) were genotyped for FTO variants rs9939609 and rs1121980, and had available PA data. PA was measured objectively using accelerometers (TracmorD, Philips), while anthropometric measures (BMI, and waist circumference; WC) were self-reported via the internet. The interaction effect of PA and FTO on anthropometric measures was evaluated using Robust Linear Regression analysis. Results. Participants mean age was 39.9 years (range 18 to 79y), 58% were women and 97% were Caucasians, with a mean BMI of 25.4 kg.m-2. Overall, 47% of the participants met the PA guidelines (=150 min.wk-1 moderate-equivalent PA). FTO genotype was associated with an increase in body weight (ß: 1.09 kg per risk allele, SE:0.5; P=0.024), BMI (ß: 0.54 kg.m-2, SE:0.2; P<0.0001) and waist circumference (WC; ß: 1.07 cm, SE: 0.4; P=0.011). Moderate-equivalent PA attenuated the effect of FTO on BMI (P for interaction = 0.020). In inactive individuals, FTO increased BMI by 1.06 units-per allele (p=0.024) whereas the increase in BMI was significantly attenuated in active individuals (0.16 units, p=0.388). We observed similar effects for WC (P for interaction = 0.005): the FTO risk allele increased WC by 2.72 cm per allele among inactive individuals but by only 0.49 cm in active individuals. Conclusion. Our results show that PA attenuates the effect of FTO genotype on BMI and WC. Our observation has important public health implications because genetic susceptibility to obesity by FTO variants may be reduced by adopting a physically active lifestyle.