Nutrigenetics and Nutrigenomics for Precision Weight-Loss Diet Interventions

摘要 在饮食干预的参与者中，减肥方面存在相当大的人际差异。传统型 一刀切的干预策略通常忽略了这种差异，导致有效性较低；然而 我们目前对影响人际变异性的内在因素的了解非常贫乏。这个 拟议的系统研究旨在填补这一重大研究空白，确定新的内置因素， 确定饮食干预中的人际变异性。在两个最大和最全面的 对流行的减肥饮食的对比试验--减肥(N=811)和直接减肥(N=322)，我们 建议在全基因组水平上识别与2年相关的新的循环microRNAs(MiRNAs) 饮食干预后的减肥效果。我们还将前瞻性地研究减肥饮食的效果。 干预不同常量营养素成分对血清miRNAs动态变化的影响 MiRNAs与调节能量摄入和消耗的标志物之间的关系。此外，我们还将申请 新开发的预测体重减轻的多重组学算法，通过将miRNAs与基因组学相结合， 代谢组学、生化和临床措施。我们已经组建了一支经验丰富的坚实的团队 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，我们的研究将为miRNAs在决定 响应饮食干预的减肥，并显著提高精确度的效率 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.