Animal Studies Investigating Molecular Transducers of Physical Activity

项目摘要 众所周知，定期体力活动，包括耐力(有氧)运动训练和 抗阻运动训练对预防和治疗众多慢性病具有重要作用 疾病。确定运动反应的分子机制或“图谱”已成为一种 生物医学研究的重要焦点。人体运动中的分子传感器 联盟(MoTrPAC)将定义构成以下巨大益处的分子足迹 在人类身上进行锻炼。此应用程序适用于临床前动物研究站点(PASS)。这支调查团队 有潜力在MoTrPAC项目的设计和执行中发挥重要作用，基于我们的 丰富的经验和良好的协作记录。第一阶段的目标是：1)提供杰出的 智力贡献和建议，并以高度合作和合作的方式与他人合作 指导委员会成员，为PASS研究设计尽可能好的实验。2.)要使用 实验室拥有广泛的专业知识来进行高度受控和准确的运动研究和 采集动物组织和血液样本。在这个阶段，大鼠已被确定为动物模型 这是最接近人类的，也是最可行的研究。运动生物学中的一个新兴概念是 体育锻炼激活了整个有机体的组织间交流，而这种组织交叉- 谈话可以调节锻炼对健康的一些有益影响。第二阶段的目标是进行 研究新的和联合体确定的参与运动的循环分子的机制研究- 受调控的组织串扰，包括鉴定分子的功能和来源。骨骼 肌肉来源的肌肉因子和脂肪组织来源的脂肪因子将被研究。第二阶段的具体目标 该项目的主要内容是：1)根据生成的数据识别新的运动调节脂肪因子和肌肉运动因子 MoTrPAC；2)确定候选肌动蛋白和脂肪因子的生理指标和功能； 3)确定运动调节的肌肉因子和脂肪因子是否对新陈代谢健康有好处 在正常和新陈代谢受损的动物中；以及4)确定假定的运动诱导的肌肉运动因子 脂肪因子是由骨骼肌和脂肪组织分泌的。这些高度创新的研究将 极大地提高了我们对体育活动改善人类健康的机制的理解 并可能为未来对抗许多慢性病的疗法提供基础。

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.