QNMR system for whole body composition analysis of live mice

描述(由申请者提供)：我们正在为EchoMRI 3合1 q核磁共振身体成分分析仪申请资金，该分析仪将允许我们在没有麻醉的情况下测量活体小鼠的身体成分(脂肪质量、瘦肉质量、游离液体、总体水)，每只小鼠大约一分钟。它还可以对解剖的组织和活组织进行脂肪、脂肪和液体分析。这些测量对于肥胖、能量稳态、营养利用和新陈代谢的其他方面的研究至关重要，这些方面是斯克里普斯几个实验室的中心重点，包括这项应用的八个用户。肥胖本身就是一种衰弱的疾病，也是导致一系列慢性疾病的主要因素，包括心脏病、2型糖尿病、高血压、关节炎、睡眠呼吸暂停和某些形式的癌症。为了阐明导致肥胖和其他代谢紊乱的生理途径，并为肥胖或肥胖相关疾病的可能治疗提供见解，我们研究了中枢神经系统调节食物摄入量和能量消耗的机制(Bartfai，Conti，Cravatt，Zorrilla)，以及决定肥胖、骨骼肌能量消耗，肝脏脂肪动态平衡和胰岛β细胞激素处理的外周途径(Cravatt，Gekakis，Kralli，Saez)。我们的方法包括对小鼠的遗传和药物操作、特殊饮食和锻炼。小鼠对美味食物和过量进食的反应与人类相似，它们会变得肥胖，对胰岛素产生抵抗力，并患上肝脏脂肪变性。我们研究的关键是能够快速和定量地测量瘦体重和脂肪体重对整体身体组成的贡献。同样关键的是测量组织和活检中的脂肪含量，因为肥胖导致的病理至少部分是由于脂肪储存在脂肪隔间之外。EchoMRI 3合1非常适合于这项任务，因为它可以在无麻醉的情况下在大约一分钟内测量脂肪和精瘦身体质量、体液和全身水分。EcoMRI 3合1是无与伦比的功能组合，使其非常适合我们的工作，包括使用活鼠的能力，测量的准确性和精确度，由于每只鼠标的快速测量而获得的高吞吐量，以及进行组织测量的能力。重要的是，EchoMRI 3合1还将与综合实验室动物监测系统(CLAMS)一起使用，该系统已经安装并在斯克里普斯小鼠行为评估核心中使用。该系统通过间接量热法测量能量消耗和呼吸商，以及食物和水的摄入量，以及自由活动小鼠的活动。食物成分和环境温度可以改变，可以增加转轮，核心体温可以通过遥测进行监测。对瘦体重进行校正是至关重要的，这样才能对不同身体成分的小鼠进行比较。

DESCRIPTION (provided by applicant): We are requesting funds for an EchoMRI 3-in-1 qNMR body composition analyzer, which will allow us to measure body composition (fat mass, lean mass, free fluids, total body water) in live mice without anesthesia, in about one minute per mouse. It also allows fat, lean, and fluid analysis of dissected tissues and biopsies. Such measurements are critical to the study of obesity, energy homeostasis, nutrient utilization, and other aspects of metabolism, which are a central focus of several laboratories at Scripps, including the eight users of this application. Obesity is a debilitating condition on its own and a major contributing factor to a host of chronic diseases, including heart disease, type 2 diabetes, hypertension, arthritis, sleep apnea, and some forms of cancer. To elucidate the physiologic pathways that contribute to obesity and other metabolic disorders, as well as provide insights into possible treatments for obesity or obesity-associated diseases, we study CNS mechanisms that regulate food intake and energy expenditure (Bartfai, Conti, Cravatt, Zorrilla), and peripheral pathways that determine adiposity, energy expenditure in skeletal muscle, lipid homeostasis in liver, and hormone processing in pancreatic beta-cells (Cravatt, Gekakis, Kralli, Saez). Our approaches include the genetic and pharmacologic manipulation of mice, special diets, and exercise. Mice respond to palatable food and over eating similarly to humans in that they become obese and insulin resistant and develop hepatic steatosis. Key to our studies is the ability to rapidly and quantitatively measure the contributions of lean and fat body mass to overall body composition. Also critical is the measurement of fat content in tissues and biopsies, as the pathologies that result from obesity are due, at least in part, to storage of fat outside of the adipose compartment. The EchoMRI 3-in-1 is ideally suited to this task as it measures fat and lean body mass, body fluids, and total body water in about a minute without anesthesia. The EcoMRI 3-in-1 is unsurpassed in the combination of features that make it ideally suited to our work, including the ability to work with live mice, the accuracy and precision of the measurements, the high throughput due to quick measurement of each mouse, and the ability to do tissue measurements. Importantly, the EchoMRI 3-in-1 will also be used in conjunction with the comprehensive laboratory animal monitoring system (CLAMS), already installed and in use in the Scripps Mouse Behavioral Assessment Core. The system measures energy expenditure and respiratory quotient via indirect calorimetry as well as food and water intake, and activity in freely moving mice. Food composition and ambient room temperature can be varied, running wheels can be added and core body temperatures can be monitored using telemetry. It is essential that these measures be corrected for lean body mass to make comparisons across mice of differing body compositions possible.