Role for the obesity-related FTO gene in the cellular sensing of amino acids

被引:136
|
作者
Gulati, Pawan [1 ,2 ]
Cheung, Man Ka [1 ,2 ]
Antrobus, Robin [3 ]
Church, Chris D. [4 ]
Harding, Heather P. [1 ,2 ]
Tung, Yi-Chun Loraine [1 ,2 ]
Rimmington, Debra [1 ,2 ]
Ma, Marcella [1 ,2 ]
Ron, David [1 ,2 ]
Lehner, Paul J. [3 ]
Ashcroft, Frances M. [5 ]
Cox, Roger D. [4 ]
Coll, Anthony P. [1 ,2 ]
O'Rahilly, Stephen [1 ,2 ]
Yeo, Giles S. H. [1 ,2 ]
机构
[1] Univ Cambridge, Metab Res Labs, Inst Metab Sci, Cambridge CB2 0QQ, England
[2] Addenbrookes Hosp, Natl Inst Hlth Res, Cambridge Biomed Res Ctr, Cambridge CB2 0QQ, England
[3] Univ Cambridge, Cambridge Inst Med Res, Dept Med, Cambridge CB2 0XY, England
[4] Med Res Council Harwell, Didcot OX11 0RD, Oxon, England
[5] Univ Oxford, Dept Physiol Anat & Genet, Henry Wellcome Ctr Gene Funct, Oxford OX1 3PT, England
基金
英国医学研究理事会; 英国惠康基金;
关键词
genetics; translation; tRNA synthetase; demethylase; TRANSFER-RNA SYNTHETASES; FOOD-INTAKE; ENERGY-INTAKE; VARIANT; MOUSE;
D O I
10.1073/pnas.1222796110
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
SNPs in the first intron of FTO (fat mass and obesity associated) are strongly associated with human obesity. While it is not yet formally established that this effect is mediated through the actions of the FTO protein itself, loss of function mutations in FTO or its murine homologue Fto result in severe growth retardation, and mice globally overexpressing FTO are obese. The mechanisms through which FTO influences growth and body composition are unknown. We describe a role for FTO in the coupling of amino acid levels to mammalian target of rapamycin complex 1 signaling. These findings suggest that FTO may influence body composition through playing a role in cellular nutrient sensing.
引用
收藏
页码:2557 / 2562
页数:6
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