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Open Access The Hidden Cost of Housing Practices: Using Noninvasive Imaging to Quantify the Metabolic Demands of Chronic Cold Stress of Laboratory Mice

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Abstract:

Laboratory mice routinely are housed at 20 to 22 °C—well below the murine thermoneutral zone of 29 to 34 °C. Chronic cold stress requires greater energy expenditure to maintain core body temperature and can lead to the failure of mouse models to emulate human physiology. We hypothesized that mice housed at ambient temperatures of 20 to 22 °C are chronically cold-stressed, have greater energy expenditure, and have high glucose utilization in brown adipose tissue. To test our hypotheses, we used indirect calorimetry to measure energy expenditure and substrate utilization in C57BL/6J and Crl:NU-Foxn1nu nude mice at routine vivarium (21 °C), intermediate (26 °C), and heated (31 °C) housing temperatures. We also examined the activation of interscapular brown adipose tissue, the primary site of nonshivering thermogenesis, via thermography and glucose uptake in this region by using positron emission tomography. Energy expenditure of mice was significantly higher at routine vivarium temperatures compared with intermediate and heated temperatures and was associated with a shift in metabolism toward glucose utilization. Brown adipose tissue showed significant activation at routine vivarium and intermediate temperatures in both hirsuite and nude mice. Crl:NU-Foxn1nu mice experienced greater cold stress than did C57BL/6J mice. Our data indicate mice housed under routine vivarium conditions are chronically cold stress. This novel use of thermography can measure cold stress in laboratory mice housed in vivaria, a key advantage over classic metabolic measurement tools. Therefore, thermography is an ideal tool to evaluate novel husbandry practices designed to alleviate murine cold stress.

Keywords: BAT; BROWN ADIPOSE TISSUE; EPR; ENTROPY PRODUCTION RATE; PET; POSITRON EMISSION TOMOGRAPHY; ROI; REGION OF INTEREST; RQ; RESPIRATORY QUOTIENT; VCO2; VOLUME OF CARBON DIOXIDE PRODUCED; VO2; VOLUME OF OXYGEN CONSUMED

Document Type: Research Article

Affiliations: 1: Department of Medical and Molecular Pharmacology, University of California Los Angeles, Los Angeles, California, USA. johndavid@mednet.ucla.edu 2: Department of Medical and Molecular Pharmacology, University of California Los Angeles, Los Angeles, California, USA

Publication date: 2013-10-01

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  • Comparative Medicine (CM), an international journal of comparative and experimental medicine, is the leading English-language publication in the field and is ranked by the Science Citation Index in the upper third of all scientific journals. The mission of CM is to disseminate high-quality, peer-reviewed information that expands biomedical knowledge and promotes human and animal health through the study of laboratory animal disease, animal models of disease, and basic biologic mechanisms related to disease in people and animals.

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