This application requests funds to upgrade and expand a Comprehensive Lab Animal Monitoring System (CLAMS) with environmental controls, which will markedly accelerate research and discovery, particularly in common metabolic disorders that include obesity, type 2 diabetes and non-alcoholic fatty liver disease. A CLAMS is utilized for indirect calorimetry of unrestrained, conscious mice, yielding quantitative measurements of oxygen consumption (VO2), carbon dioxide production (VCO2), respiratory exchange ratio - an indicator of substrate utilization - total energy expenditure, and body temperature. It also provides measures of basal locomotor activity and exercise tolerance, as well as caloric intake. Our existing CLAMS is specialized, allowing for the precise control of ambient temperature ranging from thermoneutrality (30?C) to cold (4?C). This feature is essential for the systematic quantification of thermogenesis, the capacity to generate body heat from stored energy. Mechanisms that control thermogenesis hold great promise as targets for the treatment of obesity and diabetes, but are poorly understood. The use of a CLAMS in our initial studies has revealed profound changes in energy substrate utilization and induction of thermogenesis in multiple mouse models. As a result, there is keen interest among investigators at our institution to expand the use of CLAMS in their metabolic research. Our existing CLAMS facility allows for study of only 6 mice at a time (3 control, 3 experimental). Because each experiment typically lasts for 1-2 weeks, and requires duplicate runs to increase the number of mice monitored, this has created long waiting times and difficulty with the planning and execution of protocols. The proposed expansion will allow us to monitor up to 24 mice per experiment. This capacity will provide an appropriate balance between the availability of the CLAMS and the demand for its use. Because CLAMS is an absolutely essential technology for the understanding of mouse metabolism, the proposed expansion will fulfill a critical need and increase research productivity.
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| Palmer, Colin J; Bruckner, Raphael J; Paulo, Joao A et al. (2017) Cdkal1, a type 2 diabetes susceptibility gene, regulates mitochondrial function in adipose tissue. Mol Metab 6:1212-1225 |
