title: Variation in the FTO gene influences food intake but not energy expenditure.
abstract: Polymorphisms in the FTO (fat mass- and obesity-associated) gene are associated with obesity. The mechanisms how genetic variation in this gene influences body weight are unknown. Body weight is determined by energy intake/storage and energy expenditure. In this study, we investigated whether genetic variation in FTO influences energy expenditure or food intake in carefully phenotyped subjects. In 380 German subjects, insulin sensitivity was measured by a hyperinsulinemic euglycemic clamp. Lean body mass and body fat were quantified using the bioimpedance method. Indirect calorimetry was used to estimate the metabolic rate. Food intake was assessed using food diaries (mean 11+/-1 d) in 151 subjects participating in a lifestyle intervention program to prevent diabetes. All subjects were genotyped for the FTO single nucleotide polymorphism (SNP) rs8050136. The risk allele of SNP rs8050136 was associated with higher body fat-related parameters (all p< or =0.04, additive inheritance model). Energy expenditure was not affected by the SNP. However, the risk allele of rs8050136 was significantly associated with higher energy intake (p=0.01, dominant inheritance model) during dietary restriction. Our data suggest that the increased body weight in carriers of the risk allele of FTO SNP rs8050136 is a consequence of increased food intake, but not of impaired energy expenditure.
authors.affiliation: Department of Internal Medicine, Division of Diabetology, Endocrinology, Nephrology and Angiology, Clinical Chemistry, University of Tübingen, Tübingen, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Haupt
authors.forename: C
authors.initials: C
authors.lastname: Thamer
authors.forename: H
authors.initials: H
authors.lastname: Staiger
authors.forename: O
authors.initials: O
authors.lastname: Tschritter
authors.forename: K
authors.initials: K
authors.lastname: Kirchhoff
authors.forename: F
authors.initials: F
authors.lastname: Machicao
authors.forename: H-U
authors.initials: HU
authors.lastname: Häring
authors.forename: N
authors.initials: N
authors.lastname: Stefan
authors.forename: A
authors.initials: A
authors.lastname: Fritsche
mesh_terms: D000328:Adult; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D001823:Body Composition; D002151:Calorimetry; D002153:Calorimetry, Indirect / Q000379:methods; D015930:Diet Records; D002149:Energy Intake / Q000235:genetics*; D004734:Energy Metabolism / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*
chemical_list: D007328:Insulin; D011506:Proteins; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human