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）：我们正在申请资金来获得带有硬件和跑步机（哥伦布仪器）的 Oxymax 快速系统，该系统将允许多个用户对运动小鼠的能量消耗和燃料利用率进行研究。这些测量可以同时在 8 只小鼠上进行，可以根据包括衰老、基因修饰和药物治疗在内的各种参数对运动表现进行定量评估和比较。首席研究员 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，他的团队表明，运动的这些影响和其他影响很可能在很大程度上是由燃料感应酶 AMP 激活蛋白激酶 (AMPK) 介导的。 Ruderman 实验室将使用 Oxymax 系统和跑步机来检查运动对 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中发现，目前正在其他组织中进行研究。初步数据表明，运动会急剧激活该机制，该研究将对此进行跟踪，并将探索内皮细胞特异性敲低 SIRT1、eNOS 或 LKB1 的小鼠中，该机制和运动能力是如何改变的。在与 Ruderman 小组的合作中，Cohen 博士将确定定期运动减少高脂肪高蔗糖饮食的 LDLR-/- 小鼠动脉粥样硬化的能力是否会在遗传上缺乏 SIRT1 或其他信号之一的小鼠中减弱。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。 Bhasin 博士将研究运动与雄激素补充相结合在性腺机能减退啮齿动物模型中合成代谢信号协同激活中的作用。 该仪器还将用于检查运动对患有代谢性心脏病和心肌功能障碍的小鼠产生有益影响的基础（Colucci）~随着年龄的增长，睾酮增强小鼠运动表现的能力（Bhasin 和 Jasuja）~以及肌因子肌生长抑制素的过度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啮齿类动物小脑体内葡萄糖摄取的机制。 Seldin 和 Jasuja 将对酪蛋白激酶 2 四个亚基中的三个亚基进行基因删除的小鼠进行研究。这些小鼠的特点是体脂减少、食物摄入量和体温增加以及运动能力下降。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，基于他们对运动和信号事件的共同兴趣 它产生的。