title: Lack of association of fatness-related FTO gene variants with energy expenditure or physical activity.
abstract: BACKGROUND
  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 hypothesized that AA-genotypes of rs9939609 FTO have lower energy expenditure and/or a lower level of physical activity.
  
  
  METHODS
  The study population included all obese young men (body mass index > or = 31 kg/m(2)) at the mandatory draft board examinations in the Copenhagen area from 1943 to 1977 and a randomly selected control group from this population. Subgroups of 234 obese and 323 controls were examined in 1998-2000 (median age 48 yr). Fat mass (FM), lean body mass (LBM), leisure-time physical activity (LTPA), maximum oxygen uptake (VO(2)max), resting energy expenditure (REE), and glucose-induced thermogenesis (GIT) were measured. The FTO rs9939609 variant was genotyped. A recessive transmission mode fit the data best. Logistic regression was used to assess the odds ratios of the AA-genotype in relation to LTPA, VO(2)max, 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, VO(2)max, 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, VO(2)max, 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, VO(2)max, or LTPA but higher FM, irrespective of LBM, REE, GIT, VO(2)max, and LTPA.
authors.affiliation: Institute of Preventive Medicine, Øster Søgade 18, Copenhagen K, Denmark. tb@ipm.regionh.dk
authors.forename: T
authors.initials: T
authors.lastname: Berentzen
authors.forename: S I I
authors.initials: SI
authors.lastname: Kring
authors.forename: C
authors.initials: C
authors.lastname: Holst
authors.forename: E
authors.initials: E
authors.lastname: Zimmermann
authors.forename: T
authors.initials: T
authors.lastname: Jess
authors.forename: T
authors.initials: T
authors.lastname: Hansen
authors.forename: O
authors.initials: O
authors.lastname: Pedersen
authors.forename: S
authors.initials: S
authors.lastname: Toubro
authors.forename: A
authors.initials: A
authors.lastname: Astrup
authors.forename: T I A
authors.initials: TI
authors.lastname: Sørensen
mesh_terms: D000328:Adult; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D004734:Energy Metabolism; D015444:Exercise; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010101:Oxygen Consumption; D011506:Proteins / Q000235:genetics*; D022722:Thermogenesis
chemical_list: D011506:Proteins; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human