Correspondence

Obesity, FTO Gene Variant, and Energy Intake in Children

N Engl J Med 2009; 360:1571-1572April 9, 2009

Article

To the Editor:

Cecil and colleagues (Dec. 11 issue)1 report that the A allele of the fat mass and obesity–associated (FTO) gene variant rs9939609, which has been associated with obesity, is also associated with increased levels of physical activity in children. No differences in resting energy expenditure were observed. The association between the A allele and body-mass index (BMI) was explained by a relative overconsumption of food.

The Malmö Preventive Project is a population-based study of adults from Malmö, Sweden, in which anthropometry was performed and self-reported physical activity was assessed.2 We genotyped the rs9939609 variant in 15,931 participants without diabetes and examined whether the minor A allele was associated with increased BMI and physical activity.

We found that the minor A allele was associated with an increased BMI (BMI [the weight in kilograms divided by the square of the height in meters] with the TT genotype, 24.0; 95% confidence interval [CI], 24.0 to 24.1; BMI with the TA genotype, 24.3; 95% CI, 24.2 to 24.4; BMI with the AA genotype, 24.5; 95% CI, 24.4 to 24.6; P<0.001). Moreover, after adjustment for age, sex, and BMI, the A allele was also associated with increased physical activity levels (P=0.02) (Figure 1Figure 1Association between the FTO rs9939609 Variant and Physical Activity in 15,931 Middle-Aged Swedish Men and Women.).

In summary, we confirm that carriers of the minor allele at the FTO rs9939609 gene variant, despite being at increased risk for obesity, appear to be slightly, albeit statistically significantly, more physically active than noncarriers.

Anna Jonsson, M.S.
Malmö University Hospital, 20502 Malmö, Sweden

Paul W. Franks, Ph.D., M.S.
Umeå University Hospital, 90186 Umeå, Sweden
paul.franks@medicin.umu.se

3 References

1. 1

   Cecil JE, Tavendale R, Watt P, Hetherington MM, Palmer CNA. An obesity-associated FTO gene variant and increased energy intake in children. N Engl J Med 2008;359:2558-2566
   Full Text | Web of Science | Medline

2. 2

   Berglund G, Nilsson P, Eriksson KF, et al. Long-term outcome of the Malmö Preventive Project: mortality and cardiovascular morbidity. J Intern Med 2000;247:19-29
   CrossRef | Web of Science | Medline

3. 3

   Brito EC, Lyssenko V, Renström F, et al. Previously associated type 2 diabetes variants may interact with physical activity to modify the risk of impaired glucose regulation and type 2 diabetes: a study of 16,003 Swedish adults. Diabetes (in press).
   

Author/Editor Response

The data from Jonsson and Franks indicate that the obesity-risk allele of FTO is associated with slightly greater self-reported physical activity. Their findings extend our observations in young schoolchildren, in whom we found that the FTO variant was associated with increased activity-related energy expenditure, measured directly with the use of an isotope-dilution method. Both studies suggest that the increased activity cannot be accounted for by the increased body mass of these people.

The interpretation of these observations is not straightforward. It is possible that the increased activity may be due to a behavioral adaptation whereby people may undertake additional exercise in an attempt to offset their tendency to gain weight. Another hypothesis is that the FTO variant may be a remnant of our hunter–gatherer past, representing a more global “active foraging” phenotype that drives both the preference for energy-rich foods and the vigor with which a person seeks food.

Confirmation of the association between the FTO variant and increased energy expenditure with the use of both direct measures and questionnaire data demonstrates the robust nature of the effects of FTO variants. Indeed, our findings regarding measured intake and preferential selection of energy-rich foods were also recently confirmed by a large questionnaire-based study of more than 6000 children.1

Colin N.A. Palmer, Ph.D.
University of Dundee, Dundee DD19SY, United Kingdom
nuclear-receptor@dundee.ac.uk

Jo Cecil, Ph.D.
University of St. Andrews, St. Andrews KY16 9TS, United Kingdom

Marion Hetherington, Ph.D.
University of Leeds, Leeds LS2 9JT, United Kingdom

1 References

1. 1

   Timpson NJ, Emmett PM, Frayling TM, et al. The fat mass- and obesity-associated locus and dietary intake in children. Am J Clin Nutr 2008;88:971-978
   Web of Science | Medline

Citing Articles (3)

Citing Articles

1. 1

   Steven C. Moore, Marc J. Gunter, Carrie R. Daniel, K. Srinath Reddy, Preeti S. George, Susan Yurgalevitch, Niveditha Devasenapathy, Lakshmy Ramakrishnan, Nilanjan Chatterjee, Stephen J. Chanock, Sonja I. Berndt, Aleyamma Mathew, Dorairaj Prabhakaran, Rashmi Sinha. (2011) Common Genetic Variants and Central Adiposity Among Asian-Indians. Obesity
   CrossRef

2. 2

   Yi-Chun Loraine Tung, Giles S. H. Yeo. (2011) From GWAS to biology: lessons from FTO. Annals of the New York Academy of Sciences 1220:1, 162-171
   CrossRef

3. 3

   A. Jonsson, F. Renström, V. Lyssenko, E. C. Brito, B. Isomaa, G. Berglund, P. M. Nilsson, L. Groop, P. W. Franks. (2009) Assessing the effect of interaction between an FTO variant (rs9939609) and physical activity on obesity in 15,925 Swedish and 2,511 Finnish adults. Diabetologia 52:7, 1334-1338
   CrossRef