title: Inactivation of the Fto gene protects from obesity.
abstract: Several independent, genome-wide association studies have identified a strong correlation between body mass index and polymorphisms in the human FTO gene. Common variants in the first intron define a risk allele predisposing to obesity, with homozygotes for the risk allele weighing approximately 3 kilograms more than homozygotes for the low risk allele. Nevertheless, the functional role of FTO in energy homeostasis remains elusive. Here we show that the loss of Fto in mice leads to postnatal growth retardation and a significant reduction in adipose tissue and lean body mass. The leanness of Fto-deficient mice develops as a consequence of increased energy expenditure and systemic sympathetic activation, despite decreased spontaneous locomotor activity and relative hyperphagia. Taken together, these experiments provide, to our knowledge, the first direct demonstration that Fto is functionally involved in energy homeostasis by the control of energy expenditure.
authors.affiliation: Institute for Animal Developmental and Molecular Biology, Heinrich Heine University, Universitätsstr. 1, D-40225 Düsseldorf, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Fischer
authors.forename: Linda
authors.initials: L
authors.lastname: Koch
authors.forename: Christian
authors.initials: C
authors.lastname: Emmerling
authors.forename: Jeanette
authors.initials: J
authors.lastname: Vierkotten
authors.forename: Thomas
authors.initials: T
authors.lastname: Peters
authors.forename: Jens C
authors.initials: JC
authors.lastname: Brüning
authors.forename: Ulrich
authors.initials: U
authors.lastname: Rüther
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D050154:Adiposity / Q000235:genetics; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000235:genetics; D001921:Brain / Q000378:metabolism; D004435:Eating / Q000502:physiology; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000196:embryology; D004734:Energy Metabolism / Q000235:genetics / Q000502:physiology; D005260:Female; D006130:Growth Disorders / Q000235:genetics / Q000503:physiopathology; D006720:Homozygote; D006963:Hyperphagia / Q000235:genetics; D007328:Insulin / Q000378:metabolism; D008297:Male; D051379:Mice; D006899:Mixed Function Oxygenases; D009043:Motor Activity / Q000235:genetics / Q000502:physiology; D009765:Obesity / Q000235:genetics* / Q000517:prevention & control; D007652:Oxo-Acid-Lyases / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D013564:Sympathetic Nervous System / Q000502:physiology; D013851:Thinness / Q000235:genetics*
chemical_list: D007328:Insulin; D006899:Mixed Function Oxygenases; C524916:FTO protein, mouse; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D007652:Oxo-Acid-Lyases