588.1 - Housing Temperature Alters Energy Expenditure and Adipose Tissue Bioenergetics in Mice

Daniel Sadler (Arkansas Children’s Research Institute, University of Arkansas for Medical Sciences, Arkansas Children’s Nutrition Center), Lillie Treas (Arkansas Children’s Research Institute, University of Arkansas for Medical Sciences, Arkansas Children’s Nutrition Center), Craig Porter (Arkansas Children’s Research Institute, University of Arkansas for Medical Sciences, Arkansas Children’s Nutrition Center)

Background: Sub-thermoneutral housing temperatures increase facultative thermogenesis in mice, a process which has been attributed in part to uncoupling protein 1 (UCP1). Typical vivarium temperatures (i.e., ~22-26°C) likely represent mild cold stress for mice, yet the metabolic impact of modest changes in housing temperature in mice remains unclear. Here, we determined the impact of transitioning mice from 24°C to 30°C on total energy expenditure (TEE) and adipose tissue bioenergetics.

Methods:  Male and female C57BL/6J mice were studied for 6-weeks. All mice were housed at 24°C (room temperature, RT) for two weeks, and then either remained at RT (n=16 per group, 8M/8F) or were transitioned to 30°C (thermoneutrality, TN) (n=16 per group, 8M/8F) for 4 weeks. Mice were housed in metabolic cages to determine TEE and its components via respiratory gas exchange. Interscapular brown adipose tissue (iBAT) and inguinal white adipose tissue (iWAT) were harvested at the end of the 6-week study to assess mitochondrial respiratory function by high resolution respirometry. 

Results:  Compared to RT, total daily energy expenditure (TEE) was 25% and 16% lower in males and females at TN (M: TN, 8.4±0.6 vs. RT, 11.1±1.0 kcal/day; F: TN, 8.1±0.6 vs. RT, 9.6±1.6 kcal/day;  Plt;0.05), which was partly due to a 36% and 40% decrease in basal metabolic rate (BEE) at TN (M: TN, 3.6±0.2 vs. RT, 5.6±0.8 kcal/day; F: TN, 3.2±0.2 vs. RT, 5.4±0.9 kcal/day; Plt;0.01). Wheel running distance completed by males was 50% lower at TN versus RT (Plt;0.05), and female mice ran 101% further than males at TN (Plt;0.05). iBAT depot mass was 73% and 76% greater at TN versus RT (Plt;0.01) in males and females, respectively, whereas iWAT mass was similar between conditions. At RT, total iBAT depot UCP1 protein content was 2-fold greater than that at TN (Plt;0.01). Further, iBAT depot UCP1 protein content was respectively 20- and 40-fold greater than the iWAT depot at TN and RT (Plt;0.01). However, iBAT UCP1-dependent respiration per depot was unaltered by housing temperature, whereas iWAT UCP1-dependent respiration per depot was 70% and 62% lower in males and females, respectively, at TN versus RT (Plt;0.01). Still, the absolute thermogenic capacity of UCP1 in the iBAT depot was 45- and 16-fold greater than the iWAT depot at TN and RT, respectively.

Conclusion: A modest change in housing temperature markedly alters BEE and thus TEE in mice. Cooler housing temperature (even those within the National Research Council’s guide for housing laboratory rodents) results in marked hypermetabolism and recruitment of UCP1 in both iWAT and iBAT. Despite UCP1 recruitment in iWAT, iBAT is the principal site of UCP1-dependent thermogenesis in mice housed at 24°C. These data may have important implications regarding the optimization of preclinical models of human disease.

Support or Funding Information

This study was supported by NIGMS through a Center of Biomedical Research Excellence pilot project (5P20GM109096) and R35GM142744. Support was also provided by the Arkansas Biosciences Institute and the USDA-ARS (USDA ARS 6026-51000-012-06S).