Nutrigenetics and Nutrigenomics for Precision Weight-Loss Diet Interventions

摘要 在饮食干预的参与者中，减肥存在相当大的人际差异。传统 “一刀切”的干预战略通常忽略了这种差异，导致效果较低;然而， 目前，我们对影响人际变异的内在因素的认识非常贫乏。的 拟议的系统研究旨在填补这一重大研究空白，以确定新的内在因素， 确定饮食干预中的人际差异。在两个最大和最全面的 比较流行的减肥饮食-磅损失（N=811）和直接（N=322），我们 我建议在全基因组规模上鉴定与2年内死亡相关的新型循环microRNAs（miRNAs）。 体重减轻对饮食干预的反应。我们还将前瞻性地研究减肥饮食的影响 干预不同的宏量营养素组成对血清miRNA的动态变化;并检查 miRNAs与调节能量摄入和消耗的标志物之间的关系。此外，我们将应用 新开发的多组学算法通过将miRNA与基因组学整合来预测体重减轻， 代谢组学、生物化学和临床测量。我们召集了一批经验丰富的 在营养遗传学和营养基因组学，生物信息学，饮食干预和 生物统计学我们相信，我们的研究将提供新的见解，在决定中的作用miRNAs， 减肥反应饮食干预，并有助于显着提高效率的精度 肥胖管理

Abstract Considerable interpersonal variability in weight loss exists among participants in diet interventions. Traditional one-size-fits-all intervention strategy generally neglects such variation, leading to lower effectiveness; however our currently knowledge on the intrinsic factors affecting interpersonal variability is extremely poor. The proposed systems study aims to fill this significant research gap, to identify novel in-built factors that determine interpersonal variability in diet interventions. In two of the largest and most comprehensive comparator trials on the popular weight-loss diets - POUNDS LOST (N=811) and DIRECT (N=322), we propose to identify novel circulating microRNAs (miRNAs) on whole genome scale associated with 2-year weight loss in response to diet interventions. We will also prospectively examine effects of weight-loss diet interventions varying in macronutrient compositions on dynamic changes in serum miRNAs; and examine the relations between miRNAs and markers regulating energy intake and expenditure. In addition, we will apply newly-developed multi-omics algorithm to predict weight loss, by integrating miRNAs with genomics, metabolomics, biochemical and clinical measures. We have assembled a solid group of experienced collaborators with expertise in Nutrigenetics and Nutrigenomics, bioinformatics, diet interventions and biostatistics. We believe that our study will provide novel insights into the roles of miRNAs in determining weight loss in response to diet interventions, and contribute significantly to improve efficiency of precision obesity management.