Foundational studies for precision nutrition

项目摘要 心脏代谢疾病的发病率在过去的半个世纪中飙升，尽管国家努力改善 通过普遍的饮食建议来保持健康。这种方法的一个关键限制是缺乏 考虑到饮食反应差异的基础上，个人的遗传，这是必不可少的， 精准营养的新兴领域本提案的长期目标是发展基础和 实验平台，以支持对精确营养干预措施进行深入的生物分析。客观 该提案的一个重要目的是开发一个模拟人类遗传多样性的实验遗传参考平台 转化为精确营养的模型。虽然主要依赖于发现驱动的方法， 一种假设是，公共卫生工作的一个主要失败是饮食建议的泛化， 通过将饮食建议与个人的代谢需求相匹配， 在个体和群体水平上都有很大的提高。这一假设是基于已发表和未发表的 工作基本原理是，完成这些研究将确定遗传和代谢因素以及高水平的 饮食影响不同心脏代谢健康的机制，可用于开发新的 精准营养的典范拟议的工作还将提供一个数据和样本库， 协作杂交，一个公开的小鼠遗传参考群体。核心假设是 通过追求三个目标进行测试：1）识别受饮食基因（GXD）影响的心脏代谢健康特征 2）确定调节对心脏代谢健康的饮食依赖性影响的遗传结构; （3）建立一个精确的营养范式来预测饮食对心脏代谢疾病的影响。这些目标 将使用一种新的、公开可用的小鼠遗传参考群体的创新组合进行研究。 以及与人类相关的饮食，对于这些饮食，存在关于其心脏代谢效应的大量流行病学数据。的 拟议中的研究意义重大，因为它将确定个体遗传变异对健康的影响 并确定受GxD相互作用影响的特征。也是 意义重大，因为它将提供生理反应的公共数据库和组织样本库 用于未来的分子分析，为新生的精确营养领域提供关键基础。的 该项目的预期成果是全面了解饮食如何影响心脏代谢， 实验遗传参考人群的健康，这是支持未来项目的重要第一步， 精准营养由此产生的数据将产生重要的积极影响，因为它将提供一个范例 通过以下方式向精确营养转变：a）识别受GxD反应影响的心脏代谢表型; B） 阐明对饮食的独特反应的遗传结构和高级机制; c）验证假定的 通过验证性研究的饮食反应;和d）生成GxD反应的丰富数据库和样品 供研究界使用的存储库。

PROJECT SUMMARY The incidence of cardiometabolic disease has soared during last half-century despite national efforts to improve health through universal dietary recommendations. A critical limitation of this approach is the lack of consideration given to dietary response differences based on an individual’s genetics, which is essential for the nascent field of precision nutrition. The long-term goal of this proposal is to develop the foundation and an experimental platform to support in-depth biological analyses of precision nutrition interventions. The objective of this proposal is to develop an experimental genetic reference platform that models human genetic diversity into a model for precision nutrition. Although largely relying on a discovery-driven approach, the central hypothesis is that a major failing of public health efforts has been generalization of dietary recommendations and that through matching dietary recommendations to an individual’s metabolic needs, cardiovascular health will be greatly improved at the individual and population level. This hypothesis is based on published and unpublished work. The rationale is that completion of these studies will identify genetic and metabolic factors and high-level mechanisms by which diet influences differential cardiometabolic health that can be used to develop new paradigms for precision nutrition. The proposed work will also provide a repository of data and samples from the Collaborative Cross, a publicly available mouse genetic reference population. The central hypothesis will be tested by pursuing three aims: 1) Identify cardiometabolic health traits that are influenced by gene-by-diet (GxD) interactions; 2) Determine the genetic architecture regulating diet-dependent effects on cardiometabolic health; and 3) Validate a precision nutrition paradigm to predict effects of diet on cardiometabolic disease. These aims will be pursued using an innovative combination of a novel, publicly available mouse genetic reference population and human relevant diets for which substantial epidemiological data exists on their cardiometabolic effects. The proposed research is significant because it will determine the health impact that individual genetic variation has on response to common diets and identify those characteristics that are influenced by GxD interactions. It is also significant because it will provide a public database of physiological responses and a sample repository of tissues for future molecular analyses, providing a critical foundation for the nascent field of precision nutrition. The expected outcome of this project is a comprehensive understanding of how diet influences cardiometabolic health in an experimental genetic reference population, an essential first step to support future projects in precision nutrition. The resulting data will have an important positive impact because it will provide a paradigm shift toward precision nutrition by: a) identifying cardiometabolic phenotypes influenced by GxD responses; b) elucidating the genetic architecture and high-level mechanisms of unique responses to diet; c) validating putative diet responses through confirmatory studies; and d) generating a rich database of GxD responses and a sample repository for use by the research community.