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- Title
Overexpression of Fto leads to increased food intake and results in obesity.
- Authors
Church, Chris; Moir, Lee; McMurray, Fiona; Girard, Christophe; Banks, Gareth T.; Teboul, Lydia; Wells, Sara; Brüning, Jens C.; Nolan, Patrick M.; Ashcroft, Frances M.; Cox, Roger D.
- 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.
- Subjects
INGESTION disorders; OBESITY genetics; ADIPOSE tissues; GLUCOSE intolerance; DNA; RNA; FIBROBLASTS; OBESITY in animals; DISEASE risk factors
- Publication
Nature Genetics, 2010, Vol 42, Issue 12, p1086
- ISSN
1061-4036
- Publication type
Article
- DOI
10.1038/ng.713