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This version published online on April 29, 2008
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2008-0007
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Submitted on January 3, 2008
Accepted on April 21, 2008

Lack of association of fatness-related FTO gene variants with energy expenditure or physical activity

T. Berentzen*, S. I.I. Kring, C. Holst, E. Zimmermann, T. Jess, T. Hansen, O. Pedersen, S. Toubro, A. Astrup, and T. I.A. Sørensen

Institute of Preventive Medicine, Copenhagen University Hospitals, Centre for Health and Society, Copenhagen, Denmark; Center for Pharmacogenomics, the Panum Institute, University of Copenhagen, Denmark; Steno Diabetes Centre, Gentofte, Denmark; Faculty of Health Science, University of Aarhus, Denmark; Reduce - Research Clinic of Nutrition, Hvidovre University Hospital, Denmark; Department of Human Nutrition, Faculty of Life Sciences, University of Copenhagen, Denmark

* To whom correspondence should be addressed. E-mail: tb{at}ipm.regionh.dk.

Context: A common variant in the first intron of FTO (rs9939609, T/A) is associated with fatness in Caucasians.

Objective: FTO may regulate energy homeostasis through the hypothalamus, and we hypothesize that AA-genotypes of rs9939609 FTO have lower energy expenditure (EE) and/or a lower level of physical activity (PA).

Methods: The study population included all obese young men (body mass index≥31 kg/m2) at the mandatory draft board examinations in the Copenhagen area from 1943–77, and a randomly selected control group from this population. Subgroups of 234 obese and 323 controls were examined in 1998–2000 (median age 48y). Fat mass (FM), lean body mass (LBM), leisure-time PA (LTPA), maximum oxygen uptake (VO2max), resting EE (REE) and glucose-induced thermogenesis (GIT) were measured. The FTO rs9939609 variant was genotyped. A recessive transmission mode fitted the data best. Logistic regression was used to assess the odds-ratios of the AA-genotype in relation to LTPA, VO2max, REE and GIT.

Results: The AA-genotype of FTO rs9939609 had higher REE in the age-adjusted model, but the association was eliminated when adjusting for FM and LBM. The AA-genotype was not associated with LTPA, VO2max or GIT. This was not influenced by adjustment for age, FM or LBM. The AA-genotype had increased FM even with adjustment for age, LBM, REE, GIT, VO2max and LTPA. Results were similar for FTO rs8050136 and rs7193144

Conclusions: Homozygous carriers of the A-allele of rs9939609 FTO do not have lower REE, GIT, VO2max or LTPA, but higher FM irrespective of LBM, REE, GIT, VO2max and LTPA.
Key words: FTO gene • energy expenditure • physical activity • fatness






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