QNMR system for whole body composition analysis of live mice

描述（由申请人提供）：我们正在申请一个EchoMRI三合一qNMR身体成分分析仪的资金，这将使我们能够在没有麻醉的情况下测量活体小鼠的身体成分（脂肪质量、瘦质量、游离液体、全身水分），每只小鼠大约一分钟。它还允许对解剖组织进行脂肪、瘦肉和液体分析和活组织检查。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，这是斯克里普斯几个实验室的中心焦点，包括这个应用程序的八个用户。肥胖本身是一种使人衰弱的疾病，也是导致许多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，我们研究了调节食物摄入和能量消耗的中枢神经系统机制（Bartfai, Conti, Cravatt, Zorrilla），以及决定肥胖、骨骼肌能量消耗、肝脏脂质稳态和胰腺β细胞激素处理的外周途径(Cravatt, Gekakis, Kralli，赛斯)。我们的方法包括小鼠的遗传和药理学操作，特殊饮食和运动。老鼠对美味食物和暴饮暴食的反应与人类相似，它们会变得肥胖、胰岛素抵抗，并患上肝脂肪变性。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。同样重要的是组织中脂肪含量的测量和活组织检查，因为肥胖引起的病理至少部分是由于脂肪室外的脂肪储存。EchoMRI三合一非常适合这项任务，因为它可以在没有麻醉的情况下在大约一分钟内测量脂肪和瘦体重、体液和全身水分。EcoMRI 3-in-1在功能组合方面是无与伦比的，使其非常适合我们的工作，包括与活小鼠一起工作的能力，测量的准确性和精度，由于每只小鼠的快速测量而产生的高通量，以及进行组织测量的能力。重要的是，EchoMRI三合一还将与综合实验动物监测系统（CLAMS）结合使用，该系统已经安装并在Scripps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，以及自由移动小鼠的食物和水摄入量和活动。食物成分和环境室温可以改变，跑步轮可以增加，核心体温可以用遥测技术监测。有必要根据瘦体重对这些测量进行校正，以便在不同身体组成的小鼠之间进行比较。

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.