SHEEP Request for a Metabolic Chamber System

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We are requesting funding to purchase a Comprehensive Lab Animal Monitoring System for Home Cages (CLAMS-HC) system from Columbus Instruments. The CLAMS-HC is an integrated system for the comprehensive analysis of energy balance in up to 16 animals at one time. This system collects real-time data recordings of food intake, spontaneous activity, voluntary exercise, and energy expenditure via indirect calorimetry from awake or sleeping, unrestrained animals to provide a complete energy balance profile while studying the effects of dietary and pharmacological treatments in mouse model of diseases that are highly prevalent in Veterans, including obesity, diabetes, sarcopenia, and Alzheimer’s disease. At the core of this system is a temperature-controlled cabinet that houses 16 animals in individual and sealed cages. Importantly, the CLAMS-HC system uses standard animal housing cages, avoiding confounding effects on animal behavior as a result of being placed into new cages and permitting rapid acclimation of the animals. Precise control of the fresh air flow going into the cages combined with the multiplexed detection of small differentials of oxygen and carbon dioxide coming from the interior of each cage allows for the assessment of energy expenditure by indirect calorimetry (oxygen consumption, carbon dioxide production, respiratory exchange ratio). A new generation high speed Zirconium Dioxide differential oxygen sensor combined with a nondispersive infrared sensor for carbon dioxide and a high air flow rate permit high-speed, accurate gas measurements for indirect calorimetry data with high temporal resolution and sensitivity. Animal activity is recorded with an array of infrared photo beams that surround each individual cage and detect spontaneous movements as separate beam breaks in each of the X, Y and Z axes. Optional running wheels permit the assessment of voluntary exercise. Finally, the system measures food intake by automatically calculating changes in the food weight contents of the overhead feeder. This equipment will be used to support the work of several investigators with VA Merit Award-funded research programs on diseases of high relevance to Veterans. Dr. Dudley Lamming studies how what, when, and how often we eat regulates health and longevity. He will utilize the equipment to advance his research into how the macronutrient composition of the diet – particularly, the precise amino acid composition of the dietary protein – regulate energy balance and blood glucose control. Dr. Rozalyn Anderson investigates nutrient-sensitive metabolic regulators that mediate the benefits of caloric restriction, and will examine if activating adiponectin signaling with a drug can prevent or treat the development of sarcopenia. She will use the equipment to examine how adiponectin signaling alters energy expenditure. Dr. Dawn Davis explores the intra-islet signaling mechanisms that regulate pancreatic beta cell proliferation and apoptosis, and will explore how changes in pancreatic endocrine function in her mouse models shift whole-body energy balance. Dr. Michelle Kimple studies the role of G protein coupled receptor signal transduction in pancreatic beta cell function. She will use in vivo gain and loss of function models to characterize the importance of these pathways in obesity and diabetes. Dr. Matthew Merrins studies how metabolic signaling regulates insulin secretion by the pancreatic beta cell. Dr. Mihaela Teodorescu studies the interaction of obstructive sleep apnea, energy balance and lower airway physiology. An array of ongoing and planned collaborative projects is outlined in the application, which will vastly expand the productivity and impact of these programs. All of these projects have significant implications for Veterans' health, and the CLAMS-HC system we are requesting will facilitate the progress of these productive and important projects, as well as stimulate collaborative efforts with other users.