Optimal housing temperatures for mice to mimic the thermal environment of humans: An experimental study

Abstract

ObjectivesThe laboratory mouse is presently the most common model for examining mechanisms of human physiology and disease. Housing temperatures can have a large impact on the outcome of such experiments and on their translatability to the human situation. Humans usually create for themselves a thermoneutral environment without cold stress, while laboratory mice under standard conditions (≈20° C) are under constant cold stress. In a well-cited, theoretical paper by Speakman and Keijer in Molecular Metabolism, it was argued that housing mice under close to standard conditions is the optimal way of modeling the human metabolic situation. This tenet was mainly based on the observation that humans usually display average metabolic rates of about 1.6 times basal metabolic rate. The extra heat thereby produced would also be expected to lead to a shift in the ‘lower critical temperature’ towards lower temperatures.MethodsTo examine these tenets experimentally, we performed high time-resolution indirect calorimetry at different environmental temperatures on mice acclimated to different housing temperatures.ResultsBased on the high time-resolution calorimetry analysis, we found that mice already under thermoneutral conditions display mean diurnal energy expenditure rates 1.8 times higher than basal metabolism, remarkably closely resembling the human situation. At any temperature below thermoneutrality, mice metabolism therefore exceeds the human equivalent: Mice under standard conditions display energy expenditure 3.1 times basal metabolism. The discrepancy to previous conclusions is probably attributable to earlier limitations in establishing true mouse basal metabolic rate, due to low time resolution. We also found that the fact that mean energy expenditure exceeds resting metabolic rate does not move the apparent thermoneutral zone (the lower critical temperature) downwards.ConclusionsWe show that housing mice at thermoneutrality is an advantageous step towards aligning mouse energy metabolism to human energy metabolism.

Of mice and men – environmental temperature, body temperature, and treatment of obesity

“…An interesting counter argument based on the metabolic rate range and increase below the thermoneutral region suggested that singly housed mice at 23-25°C was an appropriate model for humans [41]. A response noted that metabolic rate in a mouse at thermoneutrality ranged 1.8-fold above the BMR [42].…”

Knockout of the X‐linkedFgf13in the hypothalamic paraventricular nucleus impairs sympathetic output to brown fat and causes obesity

“…Additionally, there was reduced diurnal rhythmicity in the RER of both WT and Fgf13 +/2 animals housed at 30°C compared with 22°C housing, which has been previously observed in ref. 43. We hypothesized that the increased utilization of fat as a fuel source was due to altered behavior of the Fgf13 +/2 mice during the measurement period in metabolic cages compared with standard thermoneutral housing, possibly because of the necessity of housing the animals singly in the metabolic cages.…”

Neurofibromin is essential to maintain metabolic function and sustain life in the adult mouse

“…Most studies are conducted with cold-stressed mice due to the unique physiology of mice. This is an important variable of mouse physiology that should be considered in all studies trying to model human health and disease (44)(45)(46). The tamoxifen-inducible systemic knockout Nf1 adult model is an example where room temperature versus thermoneutral conditions alters the phenotype in an unexpected way.…”