Animal Studies Investigating Molecular Transducers of Physical Activity

项目摘要 众所周知，定期的身体活动，包括耐力（有氧）运动训练和 抗阻运动训练对预防和治疗多种慢性 疾病确定运动反应的分子机制或“地图”已成为一个重要的研究领域。 生物医学研究的重要领域。人体运动的分子转导物 联合会（MoTrPAC）将定义的分子足迹，基础上的巨大的有益效果， 在人类中锻炼。本申请适用于临床前动物研究中心（PASS）。这个调查小组 有可能在MoTrPAC项目的设计和执行中发挥重要作用， 丰富的经验和良好的合作记录。第一阶段的目标是：1）提供优秀的 智力贡献和建议，并以高度合作和合议的方式与其他工作 指导委员会的成员，为PASS研究设计最好的实验。2.）的情况。使用 实验室中各种各样的专业知识，可以进行高度受控和准确的运动研究， 收集动物组织和血液样本。对于本阶段，大鼠已被确定为动物模型 最能模仿人类也是最容易研究的运动生物学中的一个新兴概念是 体育锻炼激活了整个生物体的组织间交流，而这种组织间的交流， 谈话可以调解运动对健康的一些有益影响。第二阶段的目标是实现 机制研究，以调查新的和联盟确定的循环分子参与运动- 调节组织串扰，包括识别分子的功能和来源。骨骼 将研究肌肉来源的肌因子和脂肪组织来源的脂肪因子。第二阶段的具体目标 本项目的主要内容是：1）根据所产生的数据，鉴定新的运动调节脂肪因子和肌因子 2）确定候选肌因子和脂肪因子的生理靶点和功能; 3)确定运动调节的肌因子和脂肪因子是否对代谢健康有益 在正常和代谢受损的动物中;和4）确定假定的运动诱导的肌因子是否 脂肪因子由骨骼肌和脂肪组织分泌。这些极具创新性的研究将 大大增加了我们对身体活动改善人类健康的机制的理解 并可能为未来治疗许多慢性疾病提供基础。

PROJECT ABSTRACT It is well established that regular physical activity, including endurance (aerobic) exercise training and resistance exercise training has important effects on the prevention and treatment of numerous chronic diseases. Determining the molecular mechanisms or “map” of the exercise response has become an important focus of biomedical research. The Molecular Transducers of Physical Exercise in Humans Consortium (MoTrPAC) will define the molecular footprint that underlies the enormously beneficial effects of exercise in humans. This application is for a Preclinical Animal Study Site (PASS). This Investigative team has the potential to play an important role in the design and execution of the MoTrPAC project based on our extensive experience and strong record of collaboration. The aims of Phase 1 are: 1) To provide outstanding intellectual contributions and advice, and work in a highly cooperative and collegial manner with the other members of the Steering Committee, to design the best possible experiments for the PASS studies. 2.) To use the wide variety of expertise in the laboratory to carry out highly controlled and accurate exercise studies and collection of animal tissue and blood samples. For this Phase, the rat has been identified as the animal model that most closely mimics humans and the most feasible to study. An emerging concept in exercise biology is that physical exercise activates tissue-to-tissue communication throughout the organism, and this tissue cross- talk can mediate some of the beneficial effects of exercise on health. The goal of Phase 2 is to carry out mechanistic studies to investigate newly and Consortium-identified circulating molecules involved in exercise- regulated tissue cross-talk, including identification of the function and source of the molecules. Skeletal muscle-derived myokines and adipose tissue-derived adipokines will be studied. The Specific Aims of Phase 2 of this project are: 1) To identify novel exercise-regulated adipokines and myokines based on data generated by MoTrPAC; 2) To determine the physiological targets and functions of candidate myokines and adipokines; 3) To determine if exercise-regulated myokines and adipokines can have beneficial effects on metabolic health in normal and metabolically compromised animals; and 4) To determine if putative exercise-induced myokines and adipokines are secreted from skeletal muscle and adipose tissue. These highly innovative studies will dramatically increase our understanding of the mechanisms by which physical activity improves human health and may provide the basis for future therapeutics to combat many chronic diseases.