MoTrPAC: UC Preclinical Animal Study Site - Supplement

MoTrPAC：UC 临床前动物研究网站 - 补充材料

基本信息

批准号：
10746582
负责人：
Sue C Bodine
金额：
$ 35.66万
依托单位：
OKLAHOMA MEDICAL RESEARCH FOUNDATION
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-07-15 至 2024-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10746582
关键词：
Achievement Acute Aerobic Exercise Age Animal Experiments Animal Model Animals Body Composition California Chemicals Chronic Chronic Disease Clinical Trials Collection Complement Data Analyses Development Discipline Disease Dose Environment Epigenetic Process Evolution Exercise Exercise Physiology Exercise Test Funding Future Genetic Goals Health Health Benefit Human Indirect Calorimetry Individual Institution Insulin Knowledge Leadership Longevity Maintenance Maps Measurement Metabolic Metabolism Modeling Modification Molecular Molecular Target Morbidity - disease rate Muscle Muscle function Obesity Organ Pathway interactions Phase Phenotype Physical Fitness Physical activity Physiological Physiological Adaptation Proteomics Protocols documentation Quality of life Rattus Research Personnel Site Technology Testing Time Tissue Sample Tissues Training Transducers Universities active lifestyle adverse outcome animal data animal imaging animal model development blood glucose regulation body system cognitive function endurance exercise exercise capacity exercise intervention exercise program exercise training experience genetic technology global health heart function human model improved member metabolomics model development mortality risk novel physical inactivity pre-clinical prevent resistance exercise response skills success trait transcriptomics

项目摘要

PROJECT SUMMARY/ABSTRACT The University of California Preclinical Animal Study Site (UC PASS) is a collaborative effort between UC Davis and UC San Diego that brings together the scientific expertise, state of the art technologies and facilities, and institutional support to achieve the primary objectives goals of the PASS, which are to: 1) develop animal models that best complement the endurance and resistance training protocols used in the human trials, and 2) provide organ and tissue samples collected at multiple time points after both acute and chronic exercise for analysis by the Chemical Analysis Sites. The animal studies to be undertaken by the PASS will begin to elucidate the molecular pathways responsible for the acute and chronic effects of both endurance and resistance exercise on individual organs, as well as identify the interactions between organs; the goal being to understand the mechanisms by which different modes of physical activity impart their health benefits. In order to reach this goal, experts in model development and phenotyping of the resulting muscle and global health adaptations will be essential. The UC PASS team has exactly these traits. The team acknowledges that the ultimate animal model and exercise tests to be utilized in the PASS will be determined by the Molecular Transducers of Physical Activity Common (MoTrPAC) Steering Committee. In this application we provide a strong rationale and justification for the use of the rat as the animal model and propose specific endurance and resistance exercise programs to be used in Phase I of the PASS, highlighting the major advantages and limitations of each paradigm. In Phase II of the PASS we build on the models established in Phase I and propose three specific aims to begin to produce a standard curve of molecular transducers versus adaptive response to exercise. In Phase II we propose to exercise animals of increasing age or increasing adiposity, determine the adaptive response to 12 weeks of training, and relate this with the acute molecular transducer response to exercise. With this secondary screen, we will be able to identify molecular transducers that directly correlate with the local or global health benefits of exercise. We will then use this information to test the genetic requirement for these molecular transducers for the health benefits of exercise. The UC PASS is composed of an exceptional team of primary investigators and key collaborators/advisors with expertise in the development of animal models of exercise, the molecular response to exercise, and applied human exercise interventions. This team will provide leadership and the necessary skill sets to successfully model human exercise in animals, which is essential to the success of the MoTrPAC Common Fund and achievement of its goal: to define and understand the cellular and molecular mechanisms of the human health benefits of physical activity.

项目概要/摘要加州大学临床前动物研究中心 (UC PASS) 是加州大学与加州大学之间的合作项目戴维斯大学和加州大学圣地亚哥分校汇集了科学专业知识、最先进的技术和设施，和机构支持，以实现 PASS 的主要目标，即：1）发展动物最能补充人体试验中使用的耐力和阻力训练方案的模型，以及 2) 提供急性和慢性运动后多个时间点收集的器官和组织样本由化学分析站点进行分析。 PASS 将开始进行动物研究阐明导致耐力和耐力的急性和慢性影响的分子途径对各个器官进行抗阻训练，并确定器官之间的相互作用；目标是了解不同体育活动方式带来健康益处的机制。为了为了实现这一目标，模型开发和所得肌肉表型分析以及全球健康方面的专家适应将是必要的。 UC PASS 团队正是具备这些特质。该团队承认， PASS 中使用的最终动物模型和运动测试将由分子生物学委员会确定体力活动传感器通用 (MoTrPAC) 指导委员会。在这个应用程序中，我们提供了一个使用大鼠作为动物模型的强有力的理由和理由，并提出具体的耐力和 PASS 第一阶段将使用的阻力锻炼计划，强调了主要优点和每个范式的局限性。在 PASS 的第二阶段，我们以第一阶段建立的模型为基础，提出三个具体目标，开始制作分子传感器与自适应传感器的标准曲线对运动的反应。在第二阶段，我们建议对年龄增加或肥胖增加的动物进行锻炼，确定对 12 周训练的适应性反应，并将其与急性分子传感器联系起来对运动的反应。有了这个辅助屏幕，我们将能够识别分子传感器，直接与运动对当地或全球健康的益处相关。然后我们将使用这些信息来测试遗传运动对健康的益处需要这些分子传感器。 UC PASS 的组成包括由具有开发专业知识的主要研究者和关键合作者/顾问组成的杰出团队运动动物模型、运动的分子反应以及人类运动干预的应用。该团队将提供领导力和必要的技能，以成功模拟人体锻炼动物，这对于 MoTrPAC 共同基金的成功和实现其目标至关重要：定义和理解身体活动对人类健康有益的细胞和分子机制。