Background Variation in the fat mass and obesity–associated(FTO) gene has provided the most robust associations with commonobesity to date. However, the role of FTO variants in modulatingspecific components of energy balance is unknown.
Methods We studied 2726 Scottish children, 4 to 10 years ofage, who underwent genotyping for FTO variant rs9939609 andwere measured for height and weight. A subsample of 97 childrenwas examined for possible association of the FTO variant withadiposity, energy expenditure, and food intake.
Results In the total study group and the subsample, the A alleleof rs9939609 was associated with increased weight (P=0.003 andP=0.049, respectively) and body-mass index (P=0.003 and P=0.03,respectively). In the intensively phenotyped subsample, theA allele was also associated with increased fat mass (P=0.01)but not with lean mass. Although total and resting energy expenditureswere increased in children with the A allele (P=0.009 and P=0.03,respectively), resting energy expenditure was identical to thatpredicted for the age and weight of the child, indicating thatthere is no defect in metabolic adaptation to obesity in personsbearing the risk-associated allele. The A allele was associatedwith increased energy intake (P=0.006) independently of bodyweight. In contrast, the weight of food ingested by childrenwho had the allele was similar to that in children who did nothave the allele (P=0.82).
Conclusions The FTO variant that confers a predisposition toobesity does not appear to be involved in the regulation ofenergy expenditure but may have a role in the control of foodintake and food choice, suggesting a link to a hyperphagic phenotypeor a preference for energy-dense foods.
Source Information
From the Bute Medical School, University of St Andrews, St Andrews (J.E.C.); the Biomedical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee (R.T., C.N.A.P.); Chelsea School, University of Brighton, Brighton (P.W.); and the Department of Psychology, Glasgow Caledonian University, Glasgow (M.M.H.) — all in the United Kingdom.
Address reprint requests to Dr. Palmer at the Biomedical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Scotland DD1 9SY, United Kingdom, or at nuclear-receptor{at}dundee.ac.uk.
Tanofsky-Kraff, M., Han, J. C, Anandalingam, K., Shomaker, L. B, Columbo, K. M, Wolkoff, L. E, Kozlosky, M., Elliott, C., Ranzenhofer, L. M, Roza, C. A, Yanovski, S. Z, Yanovski, J. A
(2009). The FTO gene rs9939609 obesity-risk allele and loss of control over eating. Am. J. Clin. Nutr.
90: 1483-1488
[Abstract][Full Text]
Hardy, R., Wills, A. K., Wong, A., Elks, C. E., Wareham, N. J., Loos, R. J.F., Kuh, D., Ong, K. K.
(2009). Life course variations in the associations between FTO and MC4R gene variants and body size. Hum Mol Genet
0: ddp504v2-ddp504
[Abstract][Full Text]
Sonestedt, E., Roos, C., Gullberg, B., Ericson, U., Wirfalt, E., Orho-Melander, M.
(2009). Fat and carbohydrate intake modify the association between genetic variation in the FTO genotype and obesity. Am. J. Clin. Nutr.
90: 1418-1425
[Abstract][Full Text]
den Hoed, M., Westerterp-Plantenga, M. S, Bouwman, F. G, Mariman, E. C., Westerterp, K. R
(2009). Postprandial responses in hunger and satiety are associated with the rs9939609 single nucleotide polymorphism in FTO. Am. J. Clin. Nutr.
90: 1426-1432
[Abstract][Full Text]
Palmer, C. N.A.
(2009). Novel Insights Into the Etiology of Diabetes From Genome-Wide Association Studies. Diabetes
58: 2444-2447
[Full Text]
Cha, S., Koo, I., Park, B. L., Jeong, S., Choi, S. M., Kim, K. S., Shin, H. D., Kim, J. Y.
(2009). Genetic Effects of FTO and MC4R Polymorphisms on Body Mass in Constitutional Types. Evid Based Complement Alternat Med
0: nep162v1-nep162
[Abstract][Full Text]
Bauer, F., Elbers, C. C, Adan, R. A., Loos, R. J., Onland-Moret, N C., Grobbee, D. E, van Vliet-Ostaptchouk, J. V, Wijmenga, C., van der Schouw, Y. T
(2009). Obesity genes identified in genome-wide association studies are associated with adiposity measures and potentially with nutrient-specific food preference. Am. J. Clin. Nutr.
90: 951-959
[Abstract][Full Text]
Burch, L. R., Zhou, K., Donnelly, L. A., Doney, A. S. F., Brady, J., Goddard, C., Morris, A. D., Hansen, M. K., Palmer, C. N. A.
(2009). A Single Nucleotide Polymorphism on Exon-4 of the Gene Encoding PPAR{delta} Is Associated with Reduced Height in Adults and Children. J. Clin. Endocrinol. Metab.
94: 2587-2593
[Abstract][Full Text]
Doney, A. S.F., Dannfald, J., Kimber, C. H., Donnelly, L. A., Pearson, E., Morris, A. D., Palmer, C. N.A.
(2009). The FTO Gene Is Associated With an Atherogenic Lipid Profile and Myocardial Infarction in Patients With Type 2 Diabetes: A Genetics of Diabetes Audit and Research Study in Tayside Scotland (Go-DARTS) Study. Circ Cardiovasc Genet
2: 255-259
[Abstract][Full Text]
Pausova, Z., Syme, C., Abrahamowicz, M., Xiao, Y., Leonard, G. T., Perron, M., Richer, L., Veillette, S., Smith, G. D., Seda, O., Tremblay, J., Hamet, P., Gaudet, D., Paus, T.
(2009). A Common Variant of the FTO Gene Is Associated With Not Only Increased Adiposity but Also Elevated Blood Pressure in French Canadians. Circ Cardiovasc Genet
2: 260-269
[Abstract][Full Text]
Teng, A. C. T., Adamo, K., Tesson, F., Stewart, A. F. R.
(2009). Functional characterization of a promoter polymorphism that drives ACSL5 gene expression in skeletal muscle and associates with diet-induced weight loss. FASEB J.
23: 1705-1709
[Abstract][Full Text]
Jonsson, A., Franks, P. W., Palmer, C. N.A., Cecil, J., Hetherington, M.
(2009). Obesity, FTO Gene Variant, and Energy Intake in Children. NEJM
360: 1571-1572
[Full Text]
Leibel, R. L.
(2008). Energy In, Energy Out, and the Effects of Obesity-Related Genes. NEJM
359: 2603-2604
[Full Text]
Previous
