title: Overexpression of Fto leads to increased food intake and results in obesity.
abstract: Genome-wide association studies have identified SNPs within FTO, the human fat mass and obesity-associated gene, that are strongly associated with obesity. Individuals homozygous for the at-risk rs9939609 A allele weigh, on average, ~3 kg more than individuals with the low-risk T allele. Mice that lack FTO function and/or Fto expression display increased energy expenditure and a lean phenotype. We show here that ubiquitous overexpression of Fto leads to a dose-dependent increase in body and fat mass, irrespective of whether mice are fed a standard or a high-fat diet. Our results suggest that increased body mass results primarily from increased food intake. Mice with increased Fto expression on a high-fat diet develop glucose intolerance. This study provides the first direct evidence that increased Fto expression causes obesity in mice.
authors.affiliation: MRC Harwell, Metabolism and Inflammation, Harwell Science and Innovation Campus, Harwell, UK.
authors.forename: Chris
authors.initials: C
authors.lastname: Church
authors.forename: Lee
authors.initials: L
authors.lastname: Moir
authors.forename: Fiona
authors.initials: F
authors.lastname: McMurray
authors.forename: Christophe
authors.initials: C
authors.lastname: Girard
authors.forename: Gareth T
authors.initials: GT
authors.lastname: Banks
authors.forename: Lydia
authors.initials: L
authors.lastname: Teboul
authors.forename: Sara
authors.initials: S
authors.lastname: Wells
authors.forename: Jens C
authors.initials: JC
authors.lastname: Brüning
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Nolan
authors.forename: Frances M
authors.initials: FM
authors.lastname: Ashcroft
authors.forename: Roger D
authors.initials: RD
authors.lastname: Cox
mesh_terms: D050154:Adiposity / Q000187:drug effects / Q000235:genetics; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D000818:Animals; D019540:Area Under Curve; D001831:Body Temperature; D002940:Circadian Rhythm / Q000187:drug effects / Q000235:genetics; D004041:Dietary Fats / Q000008:administration & dosage / Q000494:pharmacology; D004734:Energy Metabolism / Q000187:drug effects / Q000235:genetics; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology*; D005260:Female; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D006706:Homeostasis / Q000235:genetics; D008297:Male; D051379:Mice; D006899:Mixed Function Oxygenases; D023421:Models, Animal; D009043:Motor Activity / Q000187:drug effects; D009765:Obesity / Q000097:blood / Q000235:genetics*; D007652:Oxo-Acid-Lyases / Q000235:genetics / Q000378:metabolism*
chemical_list: D004041:Dietary Fats; D006899:Mixed Function Oxygenases; C524916:FTO protein, mouse; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D007652:Oxo-Acid-Lyases; D005947:Glucose