MoTrPAC: UC Preclinical Animal Study Site - Supplement

项目总结/摘要 加州大学临床前动物研究中心（UC PASS）是UC 戴维斯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， 和机构的支持，以实现主要目标的目标，即：1）发展动物 最好地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） 提供在急性和慢性运动后的多个时间点收集的器官和组织样本， 化学分析网站的分析。PASS将开始进行动物研究， 阐明负责耐力和耐力的急性和慢性效应的分子途径， 对单个器官进行阻力练习，并确定器官之间的相互作用;目标是 了解不同的身体活动模式赋予其健康益处的机制。为了 为了实现这一目标，模型开发和由此产生的肌肉和全球健康的表型专家 适应将是必不可少的。UC PASS团队正是具备这些特质。小组承认， PASS中使用的最终动物模型和运动试验将由分子 身体活动通用传感器（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依据，并提出了具体的耐受性， 在PASS第一阶段使用的抗阻训练计划，突出主要优点， 每个范式的局限性。在PASS的第二阶段，我们建立在第一阶段建立的模型上， 我提出了三个具体的目标，开始产生一个标准曲线的分子传感器与自适应 对锻炼的反应。在第二阶段，我们建议增加年龄或增加肥胖的动物， 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 对锻炼的反应。有了这个次级筛选，我们将能够识别直接 与运动对当地或全球健康的益处相关。然后我们将利用这些信息来测试 运动对健康的益处需要这些分子转换器。UC PASS包括 一个由主要研究者和关键合作者/顾问组成的卓越团队，在开发方面具有专业知识 运动的动物模型，运动的分子反应，以及应用的人类运动干预。 该团队将提供领导能力和必要的技能，以成功地模拟人类运动， 动物，这对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。

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.