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

Overexpression of Fto leads to increased food intake and results in obesity.
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DOI:
10.1038/ng.713
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发表时间:
2010-12
期刊:
影响因子:
30.8
通讯作者:
--
中科院分区:
生物学1区
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全基因组关联研究已经鉴定了人类FTO基因内的SNP,其显示出与肥胖的强关联。风险rs 9939609 A等位基因纯合子的个体体重增加约3 kg。小鼠中FTO的功能和/或表达的丧失导致能量消耗增加和瘦表型。我们在这里表明,Fto的普遍过表达导致体重和脂肪量的剂量依赖性增加,无论小鼠是否喂食标准或高脂肪饮食。体重增加主要是由于食物摄入量增加。葡萄糖耐受不良随着高脂饮食中Fto表达的增加而发展。这项研究提供了第一个直接证据,表明Fto表达增加会导致小鼠肥胖。
Genome-wide association studies have identified SNPs within the human FTO gene that display a strong association with obesity. Individuals homozygous for the at-risk rs9939609 A allele weigh ~3kg more. Loss of function and/or expression of FTO in mice leads to 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 high fat diet. The increased body mass results primarily from increased food intake. Glucose intolerance develops with increased Fto expression on a high fat diet. This study provides the first direct evidence that increased Fto expression causes obesity in mice.
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