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Nat Genet. 2010 Dec;42(12):1086-92. doi: 10.1038/ng.713. Epub 2010 Nov 14.

Overexpression of Fto leads to increased food intake and results in obesity.

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1
MRC Harwell, Metabolism and Inflammation, Harwell Science and Innovation Campus, Harwell, UK.

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.

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PMID:
21076408
PMCID:
PMC3018646
DOI:
10.1038/ng.713
[Indexed for MEDLINE]
Free PMC Article

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