The mouse is widely used to study diabetes and obesity. Understanding thermal biology is essential for translating observations from mice to humans. For example, mice expend large amounts of energy to maintain body temperature, while humans do not. The thermoneutral zone (TNZ) for humans is defined as the ambient temperature (Ta) range where metabolic rate is at a minimum. Here we explore the mouse TNZ, focusing on its neglected upper boundary. Total light-phase energy expenditure (TEE) was quantitated by indirect calorimetry at various Ta, while also continuously measuring core body temperature (Tb). Broken line regression with nonlinear mixed model was used for data analysis. In wild type C57BL/6J mice, TEE decreased linearly with increasing Ta until a plateau was reached. The Ta at the break point (TNZ lower bound, called the Tlc) was 28.91 ±0.15 °C. Importantly, no increase in TEE was observed at Ta up to ∼4 °C above the Tlc. Tb was constant at cool Ta and began to rise at Ta = 28.95 ±0.12 °C. Thus, the Ta at which Tb starts to increase coincides with the Tlc and was not accompanied by an increased TEE. The generality of this unexpected observation was explored in multiple mouse models, including germline deletion of three temperature-sensing channels (TrpV1, TrpM8, TrpA1), neonatal ablation of Trpv1+ neurons, diet-induced obesity, and leptin deficiency. Over 12 cohorts (in total 66 mice), there was no difference between the Tlc and start of Tb increase (0.06 ±0.22 °C). Our novel results suggest a general property of mouse thermal physiology. Unlike humans, mouse Tb starts to increase right at the Tlc. There is no range of Tas over which both TEE and Tb are constant. The results suggest that the mouse TNZ is not the “zone” of textbooks, but rather is a fraction of a degree, a point.


V. Skop: None. J. Guo: None. N. Liu: None. C. Xiao: None. K.D. Hall: None. O. Gavrilova: None. M. Reitman: None.


National Institute of Diabetes and Digestive and Kidney Diseases (DK075063)

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at