Oxymax System with Teadmill for Quantifying Exercise in Mice

Oxymax 系统与 Teamdmill 用于量化小鼠运动

• 批准号: 8247425
• 负责人: NEIL B RUDERMAN
• 金额: $ 15.74万
• 依托单位: BOSTON MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-05-01 至 2013-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8247425
• 关键词: 5' -AMP-activated protein kinase; Acute; Adipose tissue; Age; Aging; Androgens; Aorta; Atherosclerosis; Attenuated; Body Temperature; Body fat; Cerebellum; Chronic; Data; Diet; Eating; Endothelial Cells; Endothelium; Energy Metabolism; Enzymes; Event; Exercise; Fatty acid glycerol esters; Funding; Genetic; Heart Diseases; Human; Hypogonadism; Investigation; Ischemia; Knock-out; Link; Measures; Mediating; Metabolic; Modification; Mus; Muscle; Mutation; Myocardial dysfunction; Non-Insulin-Dependent Diabetes Mellitus; Performance; Pharmacotherapy; Research; Research Personnel; Rodent; Rodent Model; Role; STK11 gene; Signal Transduction; Skeletal Muscle; Sucrose; Supplementation; System; Testosterone; Tissues; angiogenesis; base; casein kinase II; feeding; follow-up; glucose uptake; in vivo; instrument; insulin sensitivity; interest; myostatin; overexpression; response

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.

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研磨机（哥伦布仪器）的Oxymax Fast系统，该系统将允许多个用户在运动小鼠中进行能量消耗和燃料利用研究。这些措施，可以同时进行8只小鼠，将允许定量评估和比较运动性能响应于各种参数，包括老化，遗传修饰和药物治疗。PI Neil Ruderman博士率先使用运动治疗人类2型糖尿病，并首次在啮齿类动物中证明运动可急剧增加骨骼肌的胰岛素敏感性。最近，他的研究小组已经表明，这些和其他运动的影响很可能是介导的，在很大程度上，由燃料传感酶AMP激活的蛋白激酶（AMPK）。 Ruderman实验室将使用Oxymax系统和Micromills来研究运动对SIRT 1/LKB 1/AMPK/eNOS信号传导机制的急性和慢性影响，该机制最近在小鼠主动脉内皮中发现，目前正在其他组织中研究。它将跟进初步数据，表明这种机制被运动急性激活，并将探索它和运动能力如何在SIRT 1，eNOS或LKB 1的内皮细胞特异性敲低的小鼠中改变。在与Ruderman小组的合作中，Cohen博士将确定定期运动减少喂食高脂肪-高蔗糖饮食的LDLR-/-小鼠动脉粥样硬化的能力是否在遗传上缺乏SIRT 1或其他信号之一的小鼠中减弱。此外，沃尔什博士将研究这些基因改变对缺血诱导的肌肉和脂肪组织血管生成的影响。Bhasin博士将研究运动与雄激素补充剂在性腺功能减退啮齿动物模型中协同激活合成代谢信号的作用。 该仪器还将用于检查运动对代谢性心脏病和心肌功能障碍小鼠的有益作用的基础（Colucci）-睾酮随着年龄增长增强小鼠运动表现的能力（Bhasin和Jasuja）-以及肌因子肌肉生长抑制素的过表达和敲除对运动表现的影响（Bhasin和Guo）。在其他研究中，Kandror博士将研究运动增加体内啮齿动物小脑葡萄糖摄取的机制，Seldin和Jasuja博士将对酪蛋白激酶2四个亚基中三个基因缺失的小鼠进行研究。这些小鼠的特点是身体脂肪减少，食物摄入量和体温增加，运动能力下降。除了用于这些研究之外，我们预计Oxymax跑步机设备将更紧密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。