Foundational studies for precision nutrition

项目总结 尽管国家努力改善心脏代谢性疾病，但心脏代谢性疾病的发病率在过去半个世纪里仍在飙升。 通过普遍的饮食建议保持健康。这种方法的一个关键限制是缺乏 考虑到基于个体遗传的饮食反应差异，这对 精准营养领域的萌芽。这项提议的长期目标是发展基础和 支持精准营养干预的深入生物学分析的实验平台。目标是 这项提议的一部分是开发一个实验性的遗传参考平台，模拟人类遗传多样性 变成了精确营养的模型。尽管在很大程度上依赖于发现驱动的方法，但中央 假设是，公共卫生努力的一个主要失败是推广饮食建议和 通过将饮食建议与个人的新陈代谢需求相匹配，心血管健康将 在个人和人口层面都有了很大的改善。这一假设是基于已出版和未出版的 工作。理由是这些研究的完成将确定遗传和代谢因素和高水平 饮食影响差异性心脏代谢健康的机制可用于开发新的 精确营养的范例。拟议的工作还将提供数据和样本的储存库 协作性交叉，一个公开可用的小鼠遗传参考种群。中心假设将是 通过追求三个目标进行测试：1)确定受基因-饮食(GxD)影响的心脏代谢健康特征 相互作用；2)确定调节饮食依赖对心脏代谢健康影响的遗传结构； 3)验证预测饮食对心脏代谢性疾病影响的精确营养范式。这些目标 将使用一种新颖的、公开可用的小鼠遗传参考种群的创新组合来进行研究 和人类相关的饮食，有关于其心脏代谢影响的大量流行病学数据。这个 拟议的研究意义重大，因为它将确定个体基因变异对健康的影响 对常见饮食的反应，并确定那些受GxD交互作用影响的特征。它也是 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。这个 该项目的预期结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 转向精确营养：a)确定受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)验证假设 通过验证性研究的饮食反应；以及d)生成丰富的GxD反应数据库和样本 供研究团体使用的存储库。

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 This hypothesis is based on published and unpublished work.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.