Foundational studies for precision nutrition

精准营养的基础研究

• 批准号: 10410563
• 负责人: DAVID W. THREADGILL
• 金额: $ 65.3万
• 依托单位: TEXAS A&M AGRILIFE RESEARCH
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10410563
• 关键词: Address; American; Behavior; Behavior Therapy; Biological; Biological Markers; Cardiometabolic Disease; Characteristics; Communities; Data; Databases; Development; Diet; Dietary Intervention; Dietary Practices; Disease; Evaluation; Experimental Genetics; Fostering; Foundations; Future; Genes; Genetic; Genetic Markers; Genetic Variation; Genome; Genomic Segment; Goals; Health; Human; Incidence; Individual; Japanese; Measurement; Mediation; Metabolic; Mission; Modeling; Molecular; Molecular Analysis; Mus; Nutritional Study; Outcome; Patients; Phenotype; Physiological; Play; Population; Precision Health; Public Health; Publishing; Recommendation; Research; Role; Sampling; Sensitivity and Specificity; Strategic Planning; System; Testing; Tissue Banks; United States National Institutes of Health; Vegan Diet; Work; base; cardiometabolism; cardiovascular health; clinical examination; clinical phenotype; data integration; data repository; data resource; dietary; dietary guidelines; epidemiologic data; feeding; genetic analysis; genetic architecture; human model; improved; innovation; ketogentic; molecular marker; molecular phenotype; mouse genetics; novel; nutrition; obesity prevention; precision nutrition; prevent; public database; repository; response; sex; tissue resource; trait; unpublished works

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.

项目概要 尽管国家努力改善，但在过去的半个世纪中，心脏代谢疾病的发病率仍在飙升 通过普遍的饮食建议来实现健康是这种方法的一个关键限制。 考虑到基于个体遗传的饮食反应差异，这对于 该提案的长期目标是为精准营养这一新兴​​领域奠定基础和发展。 支持精准营养干预的深入生物学分析的实验平台。 该提案的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 尽管很大程度上依赖于发现驱动的方法，但核心是精准营养的模型。 假设是公共卫生努力的一个主要失败是饮食建议的泛化和 通过将饮食建议与个人的代谢需求相匹配，心血管健康将得到改善 这一假设是基于已发表和未发表的假设。 其理由是，完成这些研究将确定遗传和代谢因素以及高水平。 饮食影响不同心脏代谢健康的机制可用于开发新的 拟议的工作还将提供来自精准营养的数据和样本的存储库。 Collaborative Cross，一个公开的小鼠遗传参考群体。中心假设是。 测试所追求的三个目标：1) 确定受饮食基因 (GxD) 影响的心脏代谢健康特征 相互作用；2) 确定调节饮食依赖性对心脏代谢健康影响的遗传结构； 3) 验证精准营养范例以预测饮食对心脏代谢疾病的影响。 将使用新颖的、公开的小鼠遗传参考群体的创新组合来追求 以及与人类相关的饮食，其对心脏代谢的影响存在大量流行病学数据。 拟议的研究意义重大，因为它将确定个体遗传变异对健康的影响 对常见饮食的反应并确定受 GxD 相互作用影响的特征。 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 对于未来的分子分析，为新兴的精准营养领域提供了重要的基础。 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状况，这是支持未来项目的重要第一步 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。 通过以下方式转向精准营养：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 通过验证性研究确定饮食反应；以及 d) 生成丰富的 GxD 反应数据库和样本 供研究界使用的存储库。