Department of Molecular Biosciences, The Wenner-Gren Institute, The Arrhenius Laboratories F3, Stockholm University, SE-106 91 Stockholm, Sweden; Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, DE-20246 Hamburg, Germany.
Department of Molecular Biosciences, The Wenner-Gren Institute, The Arrhenius Laboratories F3, Stockholm University, SE-106 91 Stockholm, Sweden.
Mol Metab. 2018 Jan;7:161-170. doi: 10.1016/j.molmet.2017.10.009. Epub 2017 Oct 31.
The 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.
To examine these tenets experimentally, we performed high time-resolution indirect calorimetry at different environmental temperatures on mice acclimated to different housing temperatures.
Based 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.
We show that housing mice at thermoneutrality is an advantageous step towards aligning mouse energy metabolism to human energy metabolism.
实验鼠目前是研究人类生理学和疾病机制最常用的模型。实验鼠的饲养温度会对实验结果及其与人类情况的可转化性产生重大影响。人类通常会为自己创造一个无需冷应激的热中性环境，而实验室老鼠在标准条件下（≈20°C）则一直处于冷应激状态。在 Speakman 和 Keijer 在《分子代谢》杂志上发表的一篇备受关注的理论论文中，作者认为将老鼠饲养在接近标准条件下是模拟人类代谢情况的最佳方式。这一观点主要基于以下观察结果：人类通常显示出约为基础代谢率 1.6 倍的平均代谢率。由此产生的额外热量也预计会导致“较低临界温度”向更低温度转移。
为了通过实验检验这些观点，我们在不同的环境温度下对适应不同饲养温度的老鼠进行了高时间分辨率间接测热法实验。
基于高时间分辨率的热量分析，我们发现已经处于热中性条件下的老鼠的日间平均能量消耗率比基础代谢率高出 1.8 倍，与人类情况非常相似。在任何低于热中性的温度下，老鼠的新陈代谢都超过了人类的代谢水平：处于标准条件下的老鼠的能量消耗比基础代谢率高出 3.1 倍。与之前的结论存在差异可能归因于之前由于时间分辨率低，难以准确确定老鼠的基础代谢率。我们还发现，平均能量消耗超过静息代谢率并不会使明显的热中性区（较低临界温度）向下移动。
我们表明，将老鼠饲养在热中性条件下是使老鼠的能量代谢与人类能量代谢相一致的一个有利步骤。
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