MRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, Level 4, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Box 289, Cambridge CB2 0QQ, UK.
Diabetologia. 2013 Oct;56(10):2113-21. doi: 10.1007/s00125-013-2999-5. Epub 2013 Jul 30.
Genome-wide association studies have revealed that single-nucleotide polymorphisms in the first intron of the gene encoding fat mass and obesity-associated protein (FTO) are robustly associated with BMI and obesity. Subsequently, this association with body weight, which is replicable across multiple populations and different age groups, has been unequivocally linked to increased food intake. Although evidence from a number of animal models with perturbed FTO expression indicates a role for FTO in energy homeostasis, to date, no conclusive link has been made between the risk alleles and FTO expression or its physiological role. FTO is a nucleic acid demethylase, and a deficiency in FTO leads to a complex phenotype highlighted by postnatal growth retardation, pointing to some fundamental developmental role. Recent emerging data now points to a role for FTO in the sensing of nutrients and the regulation of translation and growth. In this review, we explore the in vivo and in vitro evidence detailing the complex biology of FTO and discuss how these might link to the regulation of body weight.
全基因组关联研究表明，编码脂肪量和肥胖相关蛋白（FTO）的基因第一内含子中的单核苷酸多态性与 BMI 和肥胖密切相关。随后，这种与体重的相关性在多个群体和不同年龄组中具有可重复性，并且与食物摄入量的增加明确相关。尽管一些 FTO 表达受到干扰的动物模型的证据表明 FTO 在能量平衡中发挥作用，但迄今为止，还没有将风险等位基因与 FTO 表达或其生理作用联系起来。FTO 是一种核酸去甲基酶，FTO 的缺乏会导致一种复杂的表型，突出表现为出生后生长迟缓，这表明 FTO 在某种基本的发育过程中起着重要作用。最近出现的新数据表明，FTO 在营养物质的感知以及翻译和生长的调节中发挥作用。在这篇综述中，我们探讨了详细描述 FTO 复杂生物学的体内和体外证据，并讨论了这些证据如何与体重调节相关。
