Oxymax System with Teadmill for Quantifying Exercise in Mice

描述(由申请人提供)：我们正在申请资金，以获得一个带有硬件和跑步机的Oxymax Fast系统(Columbus Instruments)，该系统将允许多个用户对锻炼小鼠的能量消耗和燃料利用进行研究。这些测量可以同时在8只小鼠身上进行，将允许对运动表现进行定量评估和比较，以响应包括衰老、遗传修饰和药物治疗在内的各种参数。这位名叫尼尔·鲁德曼的人率先将运动用于人类2型糖尿病的治疗，并首次在啮齿动物身上证明了运动能显著提高骨骼肌对胰岛素的敏感性。最近，他的团队表明，运动的这些和其他影响在很大程度上很可能是由燃料感应酶AMP激活的蛋白激酶(AMPK)介导的。Ruderman实验室将在跑步机上使用Oxymax系统来检测运动对SIRT1/LKB1/AMPK/eNOS信号机制的急性和慢性影响，该机制最近在小鼠主动脉内皮细胞中发现，目前正在其他组织中进行研究。它将跟进初步数据，这些数据表明运动可以迅速激活这一机制，并将探索内皮细胞特异性SIRT1、eNOS或LKB1基因敲除的小鼠的这一机制和运动能力是如何改变的。在与Ruderman团队的一项合作中，科恩博士将确定，在缺乏SIRT1或其他信号的遗传缺陷小鼠中，喂食高脂高糖饮食的LDLR-/-小鼠定期运动减轻动脉粥样硬化的能力是否会减弱。此外，沃尔什博士还将研究这些基因改变对肌肉和脂肪组织中缺血诱导的血管生成的影响。巴辛博士将研究在性腺功能低下的啮齿动物模型中，运动和补充雄激素在合成代谢信号协同激活中的作用。该仪器还将被用来检测运动对患有代谢性心脏病和心肌功能障碍的小鼠(Colucci)有益效果的基础(Bhasin和Jasuja)~以及肌肉生长因子myostatin的过度表达和敲除对运动性能的影响(Bhasin和Guo)。在其他研究中，坎德罗博士将在体内研究运动增加啮齿动物小脑葡萄糖摄取的机制，塞尔丁博士和贾苏贾博士将对酪蛋白激酶2的四个亚单位中的三个亚单位基因缺失的小鼠进行研究。这些小鼠的特点是体脂减少，食物摄入量和体温增加，运动能力降低。除了用于这些研究之外，我们预计Oxmax跑步机设备将更密切地联系使用它的研究人员的研究，基于他们对运动和它产生的信号事件的共同兴趣。

DESCRIPTION (provided by applicant): We are requesting funds to obtain an Oxymax Fast System with hardware and treadmills (Columbus Instruments) that would allow multiple users to carry out studies on energy expenditure and fuel utilization in exercising mice. Such measures, which can be performed concurrently on 8 mice, will allow quantitative assessment and comparison of exercise performance in response to a wide variety of parameters including aging, genetic modifications and drug therapy. The PI, Dr. Neil Ruderman, pioneered the use of exercise in the treatment of type 2 diabetes in humans and first demonstrated in rodents that exercise acutely increases insulin sensitivity in skeletal muscle. Most recently, his group has shown that these and other effects of exercise are very likely mediated, in great measure, by the fuel sensing enzyme AMP-activated protein kinase (AMPK). The Ruderman lab will use the Oxymax system with treadmills to examine the acute and chronic effects of exercise on the SIRT1/LKB1/AMPK/eNOS signaling mechanism that it has recently identified in the endothelium of the mouse aorta and is presently studying in other tissues. It will follow up on preliminary data suggesting that this mechanism is activated acutely by exercise and will explore how it and the capacity to exercise are altered in mice with endothelial-cell specific knockdown of SIRT1, eNOS or LKB1. In a collaborative effort with the Ruderman group, Dr. Cohen will determine whether the ability of regular exercise to diminish atherosclerosis in LDLR-/- mice fed a high fat-high sucrose diet is attenuated in mice genetically lacking SIRT1 or one of the other signals. In addition, Dr. Walsh will examine the effect of these genetic alterations on ischemia-induced angiogenesis in muscle and adipose tissue. Dr. Bhasin will examine the role of exercise in conjunction with androgen supplementation in synergistic activation of anabolic signaling in the rodent models of hypogonadism. The instrument will also be used to examine the basis for the beneficial effects of exercise in mice with metabolic heart disease and myocardial dysfunction (Colucci)~ the ability of testosterone to enhance exercise performance in mice as they age (Bhasin and Jasuja)~ and the effects of overexpression and knockout of the myokine myostatin on exercise performance ( Bhasin and Guo). In other investigations, Dr. Kandror will examine the mechanism by which exercise increases glucose uptake in the rodent cerebellum in vivo and Drs. Seldin and Jasuja will carry out studies of a mouse with genetic deletion of three of the four subunits of casein kinase 2. These mice are characterized by diminished body fat, increased food intake and body temperature and a decreased ability to exercise.In addition to its use for these studies, we anticipate the oxymax treadmill apparatus will more closely link the research of the investigators who use it, based on their common interests in both exercise and the signaling events that it produces.