143 Housing temperature dictates the sex-dependent pathophysiological and proteomic responses to burn injury in mice

Objectives/Goals: Most studies house mice at temperatures known to trigger moderate cold-induced hypermetabolism in addition to failing to consider sex as a biological variable, thereby limiting translatability. The major goal of this study was to evaluate metabolic responses to burn injury in male and female mice housed at standard and thermoneutral temperatures. Methods/Study Population: Following randomization, young male and female C57BL/6J mice (n=64; 16 per group, 50% male) were housed at room temperature (24°C; RT) or thermoneutrality (30°C; TN) for 14 days post sham or burn injury. Burn injuries involved 6.5cm2 in female mice and 8.6cm2 in male mice, translating to roughly 12.5% of the total body surface area. Energy expenditure was assessed through metabolic phenotyping, and DEXA scans (prior to injury and euthanasia) were performed to assess body composition. Semi-quantitative untargeted metabolomics were carried out on brown adipose tissue, heart, kidney, liver, plasma, spleen, and white adipose tissue. Results/Anticipated Results: Compared to TN, housing mice at RT resulted in 83% and 94% greater basal energy expenditure in male and female mice, respectively (p<0.0001 for both). Burns resulted in moderate hypermetabolism in mice housed at TN only, evidenced by ~20% increase in BEE (p = 0.037). Cachexia was greater in TN-housed mice, where males subjected to burn injury demonstrated greater BAT and WAT wasting when compared to RT housed mice (p < 0.01). At the proteomic level, RT housing masked the burn-stress response. Ingenuity pathway analysis and mitochondria-specific analyses revealed changes in the mitochondrial proteome were more pronounced in mice housed at TN compared to RT housed mice. Further, sexual dimorphisms in the global proteomic stress response to burn injury were more evident in mice housed at TN. Discussion/Significance of Impact: Housing mice below TN masks key physiological and tissue-specific proteomic responses to burn injury, thereby limiting the translational value of these models. Humanizing rodent physiology by housing mice at TN temperatures represents a tool to enhance the utility of mouse models to recapitulate stress response to burn trauma.