MoTrPAC: UC Preclinical Animal Study Site - Supplement

项目摘要/摘要 加州大学临床前动物研究网站(UC PASS)是加州大学 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， 和制度支持，以实现PASS的主要目标目标，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) 提供急性和慢性运动后多个时间点采集的器官和组织样本 由化学分析站点进行分析。通行证将进行的动物研究将开始 阐明耐力和耐力的急性和慢性影响的分子途径 对单个器官进行阻力练习，以及确定器官之间的相互作用；目标是 了解不同的体力活动模式带来健康益处的机制。按顺序 为了实现这一目标，模型开发和由此产生的肌肉与全球健康表型的专家 适应将是至关重要的。加州大学帕斯分校的团队正是具有这些特点的。该团队承认， 在PASS中使用的最终动物模型和运动测试将由分子 普通体力活动传感器(MoTrPAC)指导委员会。在此应用程序中，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，并提出特定的耐力和 阻力练习计划将用于第一阶段的通过，突出主要优势和 每种范式的局限性。在通道的第二阶段，我们在第一阶段和第二阶段建立的模型基础上进行构建 提出三个具体目标，以开始产生分子换能器与自适应的标准曲线 对运动的反应。在第二阶段，我们建议对年龄越来越大或肥胖程度越来越高的动物进行锻炼， 确定12周训练的适应性反应，并将其与急性分子换能器联系起来 对运动的反应。有了这个二级筛查，我们将能够识别直接 与运动对当地或全球的健康益处相关。然后我们将使用这些信息来测试基因 为了运动对健康的益处，这些分子换能器的需求。加州大学通行证由以下部分组成 一支由主要调查人员和具有开发专业知识的主要合作者/顾问组成的非凡团队 运动的动物模型，运动的分子反应，以及应用人类运动干预。 该团队将提供领导力和必要的技能集，以成功地模拟人体运动 动物，这对MoTrPAC共同基金的成功及其目标的实现至关重要： 定义和理解体力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.