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

被引：592

作者：

Church, Chris ^{[1
]}

Moir, Lee ^{[1
]}

McMurray, Fiona ^{[1
]}

Girard, Christophe ^{[2
]}

Banks, Gareth T. ^{[1
]}

Teboul, Lydia ^{[1
]}

Wells, Sara ^{[1
]}

Bruening, Jens C. ^{[3
]}

Nolan, Patrick M. ^{[1
]}

Ashcroft, Frances M. ^{[2
]}

Cox, Roger D. ^{[1
]}

机构：

[1] MRC Harwell, Metab & Inflammat, Harwell, Berks, England

[2] Univ Oxford, Dept Physiol Anat & Genet, Henry Wellcome Ctr Gene Funct, Oxford, England

[3] Univ Cologne, CMMC, Cologne, Germany

来源：

NATURE GENETICS | 2010年 / 42卷 / 12期

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

BODY-MASS INDEX; ENERGY-EXPENDITURE; PHYSICAL-ACTIVITY; GENE-EXPRESSION; ADULT OBESITY; FAT; VARIANTS; CHILDREN; MOUSE; POLYMORPHISMS;

D O I：

10.1038/ng.713

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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, similar to 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.

引用

页码：1086 / U147

页数：8

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