University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, and National Institute for Health Research Cambridge Biomedical Research Centre, Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom.
Proc Natl Acad Sci U S A. 2013 Feb 12;110(7):2557-62. doi: 10.1073/pnas.1222796110. Epub 2013 Jan 28.
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.
FTO（肥胖与体脂肪量相关）基因第一内含子中的单核苷酸多态性与人类肥胖密切相关。虽然尚未正式确定这种影响是通过 FTO 蛋白本身的作用介导的，但 FTO 或其鼠同源物 Fto 的功能丧失突变会导致严重的生长迟缓，而全身过表达 FTO 的小鼠则肥胖。FTO 影响生长和身体成分的机制尚不清楚。我们描述了 FTO 在将氨基酸水平与哺乳动物雷帕霉素靶蛋白复合物 1 信号偶联中的作用。这些发现表明，FTO 可能通过在细胞营养感应中发挥作用来影响身体成分。
