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.
