A Biochemical Roadmap of Exercise Signaling

运动信号的生化路线图

基本信息

批准号：
10318083
负责人：
STEVEN A CARR
金额：
$ 165.12万
依托单位：
BROAD INSTITUTE, INC.
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-12-14 至 2024-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10318083
关键词：
Adipocytes Aminoisobutyric Acids Animal Model Animals Biochemical Blood Blood specimen Cardiometabolic Disease Chronic Clinical Cohort Studies Collaborations Communities Coupled Data Data Analyses Data Set Dietary Intervention Disease Exercise Framingham Heart Study Future Generations Genes Genetic Genetic Determinism Genome Scan Genomics Goals Health Benefit Heart Diseases Human In Vitro Individual Institutes Investigation Mediating Mediator of activation protein Meta-Analysis Metabolic Metabolic Diseases Molecular Molecular Profiling Monitor Multiomic Data Mus Organ Outcome Phenotype Physical activity Plasma Positioning Attribute Post-Translational Protein Processing Prevention Proteins Proteomics Records Regimen Research Research Personnel Resources Risk Factors Sampling Signal Transduction System Technology Therapeutic Intervention Time Tissue Sample Tissues Training Programs United States National Institutes of Health Weight Gain Work analytical tool base biochemical tools cardiometabolism cohort data integration data portal design diabetes prevention program disease phenotype effective intervention exercise intervention exercise training experience experimental study glucose disposal human disease human model human tissue improved informatics tool insight member metabolomics multidisciplinary multiple omics novel novel therapeutics programs protein metabolite protein profiling proteomic signature response small molecule tool

项目摘要

Project Summary/Abstract Exercise is an effective intervention for both the prevention and treatment of cardiometabolic diseases, but the mechanistic underpinnings of the health benefits of exercise remain incompletely defined. Recent work highlights the importance of inter-organ circuits in mediating healthful exercise responses. We identified β- aminoisobutyric acid (BAIBA) as a novel small molecule “myokine” that increases the expression of brown adipocyte-specific genes in vitro, and improves glucose disposal and decreases weight gain in mice. In humans, plasma BAIBA concentrations are increased with chronic exercise and demonstrate a strong inverse association with metabolic risk factors. Our team has also been a leader in characterizing within-tissue responses to exercise and dietary interventions. These experiences, coupled with the high translational relevance of the research problem, motivate us to take a systems wide approach to studying the health benefits of exercise in humans and animal models. To this end, we have formed a multi-institutional, multi-omics center to engage in collaborative studies under the aegis of the NIH MoTrPAC initiative. Our core builds upon ongoing collaborations between teams at Duke, Harvard and the Broad Institute with complementary strengths in metabolomics and proteomics technologies and decades of experience in cardiometabolic research. The core will provide a deep menu of analytical tools for targeted and non-targeted metabolomics, protein profiling, and the analysis of key protein post-translational modifications. Each of the core components has a track record for handling large sample sets, and is well- poised to analyze the expected tens of thousands of tissue and blood samples generated by a national consortium of investigators studying exercise interventions in animal and human cohorts. An additional distinction of our team is the ability to integrate new findings from MoTrPAC with previously collected genomic, proteomic and metabolomic data from large human cohorts. We hypothesize that integrating the metabolomic and proteomic profiles of human tissues and blood during exercise with genetics and detailed human phenotyping will provide novel insights into the inter-organ circuits and within-organ responses that mediate the salutary effects of exercise. All of the primary data generated by this multi- disciplinary proposal will be made rapidly available to the scientific community via a novel information portal at the Broad Institute. Importantly, all four leaders of this proposed core (Carr, Clish, Gerszten and Newgard) have strong track records in the use of metabolomics and proteomics tools for the identification of novel cardiometabolic regulatory and disease mechanisms. These experiences position this proposed core as one that can have maximal impact on the generation, analysis, and interpretation of molecular profiling data.

项目概要/摘要运动是预防和治疗心脏代谢疾病的有效干预措施，但运动对健康有益的机制基础尚未完全确定。强调了器官间回路在调节健康运动反应中的重要性我们确定了 β-。氨基异丁酸（BAIBA）作为一种新型小分子“肌因子”，可增加棕色表达体外脂肪细胞特异性基因，可改善小鼠的葡萄糖处理并减少体重增加。人类中，血浆 BAIBA 浓度随着长期运动而增加，并表现出强烈的反比我们的团队在组织内表征方面也处于领先地位。对运动和饮食干预的反应。这些经验，加上研究问题的高度转化相关性，激励我们采取一种在人类和动物模型中研究运动对健康益处的系统范围的方法。最后，我们成立了一个多机构、多组学中心，在其支持下进行合作研究 NIH MoTrPAC 计划的核心建立在杜克大学和哈佛大学团队之间的持续合作之上。和布罗德研究所在代谢组学和蛋白质组学技术方面具有互补优势数十年的心脏代谢研究经验将为该核心提供一系列深入的分析工具。靶向和非靶向代谢组学、蛋白质分析以及关键蛋白质翻译后分析每个核心组件都有处理大型样本集的记录，并且性能良好。准备分析国家实验室产生的预计数以万计的组织和血液样本研究动物和人类运动干预的研究人员联盟。我们团队的另一个特点是能够将 MoTrPAC 的新发现与之前的发现相结合从大型人类群体中收集了基因组、蛋白质组和代谢组数据。将运动过程中人体组织和血液的代谢组学和蛋白质组学特征与遗传学相结合详细的人类表型分析将为器官间回路和器官内提供新的见解调节运动有益效果的所有主要数据均由该多项生成。学科提案将通过一个新颖的信息门户网站快速提供给科学界：重要的是，这个提议的核心的所有四位领导人（卡尔、克利什、格斯坦和纽加德）。在使用代谢组学和蛋白质组学工具来鉴定新化合物方面拥有良好的记录这些经验将这一提议的核心定位为一个。这可以对分子分析数据的生成、分析和解释产生最大的影响。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Sexual dimorphism and the multi-omic response to exercise training in rat subcutaneous white adipose tissue.

大鼠皮下白色脂肪组织的性别二态性和运动训练的多组学反应。

DOI：
发表时间：
2024-05-01
期刊：
影响因子：
20.8
作者：
Many, Gina M;Sanford, James A;Sagendorf, Tyler J;Hou, Zhenxin;Nigro, Pasquale;Whytock, Katie L;Amar, David;Caputo, Tiziana;Gay, Nicole R;Gaul, David A;Hirshman, Michael F;Jimenez;Lindholm, Malene E;Muehlbauer, Michael J;Vamvin
通讯作者：
Vamvin

Exercise, exerkines, and cardiometabolic health: from individual players to a team sport.

锻炼、运动和心脏代谢健康：从个人运动员到团队运动。