LabMaster: Calo/Dri-Fed/Act.XYZ/Wheel 16 Mice/Rats

描述(申请人提供)：肥胖和糖尿病是一种复杂的疾病，已成为全球范围内的主要健康问题。这些疾病在发病机制和代谢后果方面固有的复杂性增加了对互动研究小组的需求，这些小组将多学科方法与重叠的研究兴趣结合起来。这项提议的目标是为五名密切互动的研究人员提供一个全面的、最先进的资源，用于与营养、肥胖、糖尿病或相关疾病相关的啮齿动物模型的能量平衡/代谢表型鉴定。每个研究人员都是由NIH资助的，并使用小鼠和/或大鼠模型来研究肥胖、炎症性厌食、胰岛素抵抗和代谢功能障碍的发病机制，每个研究人员都有明确的要求，以提高代谢分析能力。满足这一需求将通过购买TSE LabMaster/PhenoMaster(TSE Systems，Midland，MI)设备来实现，该设备提供了许多优于啮齿动物代谢表型鉴定的替代系统。该系统提供了一系列与啮齿动物能量代谢有关的相关措施，可同时在16只大鼠或小鼠身上进行。间接量热法通过监测进入和离开燃烧室的气体浓度并计算它们之间的差值来监测氧气消耗和二氧化碳产生的速率。这些信息反过来又产生了氧气消耗率(VO2，一种衡量能量消耗的指标)、二氧化碳产生(VCO2)、产热量和呼吸交换率(RER，也称为呼吸商，描述了作为动物燃料来源的脂肪和碳水化合物的相对氧化)的测量结果。结合运动活动、车轮运行活动和体温的同步测量(通过遥测)，该系统不仅提供了总能量消耗的测量，而且还澄清了能量消耗的差异是由于体温、体力活动、代谢率的变化，还是这些变化的某种组合。此外，对量热数据进行标准化的最佳参数是瘦体重，这将使用我们从Echo Medical Systems购买的两个最先进的磁共振波谱(MRS)设备之一(一个用于大鼠，另一个用于小鼠)来确定每种动物的瘦体重，并将其安置在TSE热量测量仪器所在的邻近空间。最后，该系统还提供食物和液体摄入量的实时测量，从而能够对能量摄入量(包括膳食模式)以及能量消耗进行定量分析。因此，这个系统提供了全面的、定量的信息，对于肥胖和糖尿病的啮齿动物模型的代谢表型至关重要。 与公共健康相关：在美国和其他发达国家，肥胖症的流行已经达到了流行的程度，并与2型糖尿病患病率在全球范围内的急剧上升存在因果关系。尽管有重大的技术进步，包括在啮齿动物模型中应用遗传、生理和药理学工具，但这些常见代谢疾病的发病机制仍然知之甚少，治疗选择也有限。目前的提案旨在支持由一组互动的、由NIH资助的研究人员对肥胖和相关疾病的啮齿动物模型进行定量代谢表型鉴定，他们很快将搬迁到一个新的研究设施。获得所需设备将极大地提高该小组进行研究的能力，并将支持具有不同但重叠兴趣的调查人员之间的协同互动。

DESCRIPTION (provided by applicant): Obesity and diabetes are complex disorders that have emerged as major health concerns worldwide. The complexity inherent in these disorders with respect both to their pathogenesis and metabolic consequences has heightened the need for interactive groups of investigators that unite multidisciplinary approaches with overlapping research interests. The goal of this proposal is to provide a group of five closely interacting investigators with a comprehensive, state-of-the-art resource for energy balance/metabolic phenotyping of rodent models relevant to nutrition, obesity, diabetes or related disorders. Each investigator is NIH-funded and employs mouse and/or rat models to investigate the pathogenesis of obesity, inflammatory anorexia, insulin resistance and metabolic dysfunction, and each has a well-defined requirement for improved metabolic analysis capability. Meeting this need will be accomplished through the purchase of the TSE LabMaster / PhenoMaster (TSE Systems, Midland, MI) apparatus, which offers numerous advantages over alternative systems for rodent metabolic phenotyping. This system provides a series of interrelated measures pertinent to rodent energy metabolism in up to 16 rats or mice simultaneously. Indirect calorimetry is used to monitor rates of oxygen consumption and carbon dioxide production by monitoring gas concentrations entering and exiting the chamber and computing the difference between them. This information in turn yields measures of the rates of oxygen consumption (VO2, a measure of energy expenditure), CO2 production (VCO2), heat production, and respiratory exchange ratio (RER, also known as respiratory quotient, which describes the relative oxidation of fat versus carbohydrate as a source of fuel by the animal). Combined with simultaneous measures of locomotor activity, wheel running activity, and body temperature (by telemetry), this system provides not only measures of total energy expenditure, but clarifies whether differences in energy expenditure are due to changes of body temperature, physical activity, metabolic rate, or some combination of these. Moreover, the optimal parameter for normalizing calorimetry data is lean body mass, and this will be determined for each animal using one of our two state-of-the-art magnetic resonance spectroscopy (MRS) units (one for rats, the other for mice) purchased from Echo Medical Systems and housed in space adjacent to where the TSE calorimetry apparatus will be located. Lastly, this system also offers real-time measures of food and liquid intake, allowing quantitative analysis of energy intake (including meal patterning), as well as energy expenditure. This system, therefore, provides comprehensive, quantitative information that is critical for metabolic phenotyping of rodent models of obesity and diabetes. PUBLIC HEALTH RELEVANCE: The prevalence of obesity has reached epidemic proportions in the US and other developed countries, and is causally linked to a dramatic, global increase in the prevalence of type 2 diabetes. Despite major technological advances, including the application of genetic, physiological and pharmacological tools in rodent models, the pathogenesis of these common metabolic disorders remains poorly understood, and treatment options are limited. The current proposal is intended to support quantitative metabolic phenotyping of rodent models of obesity and related disorders undertaken by a group of interactive, NIH-funded investigators who will soon relocate to a new research facility. Obtaining the requested equipment will critically advance the ability of this group to conduct their studies and will support synergistic interactions between investigators with distinct but overlapping interests.