Kühn Anne B, Feis Delia-Lisa, Schilbach Leonhard, Kracht Lutz, Hess Martin E, Mauer Jan, Brüning Jens C, Tittgemeyer Marc
Max Planck Institute for Metabolism Research, 50931 Cologne, Germany; Center for Endocrinology, Diabetes and Preventive Medicine (CEDP), University Hospital of Cologne, 50931 Cologne, Germany.
Max Planck Institute for Metabolism Research, 50931 Cologne, Germany.
Neuroimage. 2016 Mar;128:21-31. doi: 10.1016/j.neuroimage.2015.12.049. Epub 2016 Jan 5.
Variations in the fat mass and obesity associated (FTO) gene are currently the strongest known genetic factor predisposing humans to non-monogenic obesity. Recent experiments have linked these variants to a broad spectrum of behavioural alterations, including food choice and substance abuse. Yet, the underlying neurobiological mechanisms by which these genetic variations influence body weight remain elusive. Here, we explore the brain structural substrate of the obesity-predisposing rs9939609 T/A variant of the FTO gene in non-obese subjects by means of multivariate classification and use fMRI to investigate genotype-specific differences in neural food-cue reactivity by analysing correlates of a visual food perception task. Our findings demonstrate that MRI-derived measures of morphology along middle and posterior fusiform gyrus (FFG) are highly predictive for FTO at-risk allele carriers, who also show enhanced neural responses elicited by food cues in the same posterior FFG area. In brief, these findings provide first-time evidence for FTO-specific differences in both brain structure and function already in non-obese individuals, thereby contributing to a mechanistic understanding of why FTO is a predisposing factor for obesity.
脂肪量和肥胖相关基因(FTO)的变异目前是已知最强的使人类易患非单基因肥胖的遗传因素。最近的实验已将这些变异与广泛的行为改变联系起来,包括食物选择和药物滥用。然而,这些基因变异影响体重的潜在神经生物学机制仍不清楚。在此,我们通过多变量分类方法,探究非肥胖受试者中FTO基因肥胖易感性rs9939609 T/A变异的脑结构基础,并利用功能磁共振成像(fMRI),通过分析视觉食物感知任务的相关性,研究神经食物线索反应性的基因型特异性差异。我们的研究结果表明,沿中梭状回和后梭状回(FFG)的磁共振成像形态学测量对FTO风险等位基因携带者具有高度预测性,这些携带者在相同的后FFG区域也表现出由食物线索引发的增强神经反应。简而言之,这些发现首次为非肥胖个体中FTO在脑结构和功能上的特异性差异提供了证据,从而有助于从机制上理解为什么FTO是肥胖的一个易感因素。