Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA.
Laboratory of Biological Modeling, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA.
Cell Rep. 2020 Apr 14;31(2):107501. doi: 10.1016/j.celrep.2020.03.065.
Human and mouse thermal physiology differ due to dissimilar body sizes. Unexpectedly, in mice we found no ambient temperature zone where both metabolic rate and body temperature were constant. Body temperature began increasing once cold-induced thermogenesis was no longer required. This result reproduced in male, female, C57BL/6J, 129, chow-fed, diet-induced obese, and ob/ob mice as well as Trpv1;Trpm8;Trpa1 mice lacking thermal sensory channels. During the resting-light phase, the energy expenditure minimum spanned ∼4°C of ambient temperature, whereas in the active-dark phase it approximated a point. We propose the concept of a thermoneutral point (TNP), a discrete ambient temperature below which energy expenditure increases and above which body temperature increases. Humans do not have a TNP. As studied, the mouse TNP is ∼29°C in light phase and ∼33°C in dark phase. These observations inform how thermoneutrality is defined and how mice are used to model human energy physiology and drug development.
人类和小鼠的热生理学因体型不同而存在差异。出乎意料的是,我们发现小鼠在任何环境温度下,代谢率和体温都不会保持恒定。一旦不再需要冷诱导产热,体温就开始上升。这一结果在雄性、雌性、C57BL/6J、129、普通饮食、饮食诱导肥胖以及缺失热感觉通道的 TRPV1;TRPM8;TRPA1 小鼠中得到重现。在休息-光照阶段,能量消耗最小值跨越了约 4°C 的环境温度,而在活动-黑暗阶段则接近一个点。我们提出了一个热中性点(TNP)的概念,即一个离散的环境温度,低于这个温度,能量消耗增加,高于这个温度,体温增加。人类没有 TNP。如研究所示,小鼠在光照阶段的 TNP 约为 29°C,在黑暗阶段约为 33°C。这些观察结果为如何定义热中性以及如何使用小鼠来模拟人类能量生理学和药物开发提供了信息。