Metabolic Research Labs, Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge Cambridge, UK.
Front Endocrinol (Lausanne). 2011 Feb 22;2:4. doi: 10.3389/fendo.2011.00004. eCollection 2011.
Few would dispute that the current obesity epidemic has been driven by lifestyle and environmental changes. However, it is clear that individuals respond differently to these "obesigenic" changes and this variation in response has a strong genetic element. Genome-wide association studies have revealed that single nucleotide polymorphisms in Fat mass and obesity-associated transcript (FTO) are robustly associated with body mass index and obesity. Although the effect of these risk alleles are modest, with heterozygous and homozygous carriers weighing approximately 1.5 and 3 kg more respectively, there are an estimated one billion homozygous carriers in the world, spanning multiple different ethnicities and populations. Yet despite its broad impact, the biological function of FTO, particularly its role in controlling energy balance, remains unknown. Although the study of severe Mendelian obesity has been invaluable in illuminating critical pathways controlling food intake, the major burden of disease is carried by those of us with "common obesity," which to date has resisted yielding meaningful biological insights. FTO has at last given us a handle on a huge, worldwide, common problem. In this review, we focus on the available genetic and in vivo evidence to date that implicates FTO in the control of energy balance.
很少有人会质疑，当前的肥胖症流行是由生活方式和环境变化所驱动的。然而，很明显，个体对这些“致肥胖”的变化有不同的反应，这种反应的差异有很强的遗传因素。全基因组关联研究表明，脂肪量和肥胖相关转录物（FTO）中的单核苷酸多态性与体重指数和肥胖密切相关。尽管这些风险等位基因的影响较小，杂合子和纯合子携带者的体重分别增加约 1.5 公斤和 3 公斤，但据估计，全球有 10 亿纯合子携带者，分布在多个不同的种族和人群中。尽管它的影响广泛，但 FTO 的生物学功能，特别是它在控制能量平衡方面的作用，仍然未知。尽管严重的孟德尔肥胖症的研究对于阐明控制食物摄入的关键途径非常有价值，但疾病的主要负担是由那些患有“普通肥胖症”的人承担的，迄今为止，普通肥胖症还没有为我们提供有意义的生物学见解。FTO 终于让我们找到了一个全球性的、普遍存在的、巨大的问题的解决方法。在这篇综述中，我们重点介绍了迄今为止与 FTO 控制能量平衡有关的遗传和体内证据。
