The study of obesity, nutrition, and metabolism relies on methods to measure feeding patterns, metabolic rate, activity, body composition, and fat distribution. Model organisms are a mainstay in the study of metabolism, obesity, and its consequences. Laboratory mice are the most fundamental and common models for studying in vivo physiology and disease pathophysiology, and the UCSF NORC Biomedical Mouse Metabolism Core (Core B) is specifically geared to measure a wide variety of metabolic parameters in mice, as well as in mouse and human tissues, and in cultured cells. The information gained by studying mice, which are often genetically modified through use of Core C (Genetics and Genomics) and examined in conjunction with epidemiological and behavioral studies done in humans (Core A), is essential to understand mechanisms underlying metabolic disease risk, and the potential effectiveness of nutritional and pharmacologic approaches to ameliorate obesity and its consequences. 21 of the 58 investigators in the proposed UCSF-NORC currently conduct research studies in which rodent models are monitored using the types of equipment and analytical approaches housed in Core B. Another 4 NORC investigators indicate that their research has developed to a point where their use of facilities in Core B is imminent. Experts in charge of running Core B keep abreast of the rapidly evolving application of these sophisticated methods, and ensure that NORC researchers are trained in their proper implementation. The presence of the facilities, and the availability of NORC support that is designed to assist the entry of NORC researchers into technologically unfamiliar areas, ensure the success of UCSF-NORC research. Core B provides access to, assistance with, and training in the use of sophisticated methods and instruments for those studies. Specifically, Core B provides tools and facilities for: 1. Precise and real-time measurement of feeding, energy expenditure, locomotor activities, respiratory exchange ratio, and thermoregulation in conscious mice. 2. Analyzing lean mass, fat mass, free and total body water in conscious mice, as well as bone mineral density and other aspects of body composition in anesthetized mice. 3. Cellular energetic measurements using the Seahorse FX24 Bioanalyzer, which measures the oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) of live cells and tissues in a 24-well plate format. OCR and ECAR are key indicators of mitochondrial respiration and glycolysis, and provide a systems- level view of cellular metabolic function in cells and ex-vivo tissue samples from model organisms and humans. 4. Equipment for urine and fecal collection and blood pressure measurement. 5. Rodent incubators that allow for the study of mice under cold ambient or warm thermoneutral conditions. 6. Gnotobiotics service. Gnotobiotic technology enables breeding and maintenance of germ-free animals devoid of any associated microorganisms, including bacteria, archaea, microscopic fungi, parasites, and viruses. Most importantly, Core B provides non-invasive methods that permit mice to be followed over time. The ability to conduct longitudinal studies in mice is particularly significant for tracking the changes in body composition, feeding behavior, and metabolic activity that both trigger and respond to the development of obesity and its associated complications. Overall, this Core significantly lowers the methodologic barriers to help NORC researchers achieve the efficient and proper application of a series of highly sophisticated tools. These tools accelerate a variety of diverse and interrelated studies in obesity, nutrition, ingestive behavior, and metabolism.
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