This application for the SHARED INSTRUMENTATION GRANT PROGRAM (SIG) NIH PAR-18-600 proposes to established a metabolic phenotyping suite outfitted with 16 state-of-the-art Sable Promethion Metabolic Cages capable of performing adult and neonatal whole body phenotyping by synchronizing metabolic and behavioral information. The non-sealed open-housing cage design allows for experimental maneuvers to be performed, e.g., drug administration, diet changes, environmental enrichment, etc. during the experimental period without interrupting data collection, and facilitiates studies in a wide variety of disease and physical disability models. In addition, the housing environment with included enrichment, minimizes needed acclimation times, as the housing environment is similar to the typical small rodent housing the animals are accustomed to, thus maximizing the number of studies performed per unit time per cage, resulting in not only cost benefits, but also significantly higher data throughput. The Promethion System?s high temporal resolution and continuous, rapid data acquisition features allow an animal?s interaction with each sensor to be recorded precisely in time and quantified in ways unique to that sensor. The parameters monitored include food and water intake, activity (wheel and ambulatory running), body weight, body mass, water loss, metabolic activity (O2 consumption and CO2 release), calorimetry, and RQ (marker for fat reserve use and/or carbohydrate catabolism). The system?s software perfectly synchronizes all data collected, leaving it to the investigator to determine which dataset interactions are most relevant to their research question. In addition, time and locomotion budgets, circadian behavioral profiling, and behavioral transition probability matrices can be produced as part of data analysis. The availability of the System to Yale investigators will open a new ?arm? of preliminary data for grant applications and facilitiate completion of funded grant applications. Another benefit to the research community is the experience of the Core staff in conducting whole body physiological studies. As shown in the application, Dr. Diano and Dr. Kim have many years of experiences doing such studies, most of which have been supported by the NIH. Both of them are committed to facilitating the use of the Core by Yale investigators. The Core will ensure equal access to all Yale investigators interested in metabolic phenotyping. If capacity allows, service will be available to external customers. Although there is currently such an instrument here at Yale it has recently become inoperable and is no longer serviceable by the company. In conlcusion, these sensitive and high-throughput analyses by the 16 state-of-the-art Sable Promethion Metabolic Cages will introduce a highly valuable approach for developing a greater understanding of pathways that regulate metabolism, and for developing therapies to target metabolic disorders.
The requested Sable Promethion metabolic cage system will permit high resolution analyses of whole body metabolism. This, in turn, will enable investigators at Yale University to better understand pathways regulating metabolism and to identify targets to prevent and/or combat metabolic disorders. This equipment will be located in a dedicated room of the Yale Animal Resource Center (YARC) and will be managed via a core facility directed by Dr. Diano and Dr. Kim, who have many years of experience both in studying metabolism and in managing the old TSE metabolic cages.