What can body temperature tell us about energy homeostasis?

哺乳动物的体温是高度调节的。然而，较小哺乳动物(如老鼠)的热生物学与较大哺乳动物(如成年人类)的热生物学不同。例如，当小鼠被单独安置在室温下时，大约一半的卡路里摄入量被燃烧以维持体温(称为冷诱导产热)，而人类几乎不需要冷诱导产热。禁食后，老鼠的体温可以降低10摄氏度，而极度饥饿的人类只会降低0.2摄氏度。 我们正在探索使用体温作为小鼠可感知的代谢状态的指示器。例如，基因操作或药物治疗对体温有什么影响？哪些基因操作或药物治疗会导致体温与营养状态分离？涉及的神经递质和神经机制是什么？ 小鼠也是研究体温过低的理想模型系统，因为中枢调节机制在哺乳动物中很可能是保守的，但小鼠表现出比大型哺乳动物更大的变化。因此，老鼠是一种更敏感的物种，可以建议在成年人类等体型较大的个体上进行富有成效的研究。我们感兴趣的是体温和体温的神经控制，以及了解体温过低的药物诱因。 2021-22财年的进展包括： 了解小鼠的热生理有助于将小鼠作为人类疾病的模型。人们普遍认为，老鼠的尾巴对热量损失有很大贡献(就像在大鼠身上一样)，但这一点还没有得到量化。我们研究了C57BL/6J小鼠断尾后的情况。在22摄氏度下饲养的无尾小鼠在体重、瘦肉或脂肪含量或能量消耗方面与产仔对照组没有区别。在环境温度从19摄氏度到39摄氏度的剧烈变化中，无尾小鼠和对照组小鼠表现出相似的体温(Tb)、代谢率和导热系数，并且在温度中和点上没有差异。用1-肾上腺素能拮抗剂和血管扩张剂哌唑嗪处理后，对照组小鼠的尾部温度增加了4.8℃，0.8℃。比较无尾小鼠和对照组小鼠的尾部温度，发现尾巴对总热量损失的贡献不显著，为3.4%。3-肾上腺素能激动剂CL316243在30℃处理产生的主要热应激增加了代谢率和Tb，在代谢率相应增加的情况下，无尾小鼠的Tb增加了0.72~0.14℃，全身热导降低了7.6%。因此，小鼠的尾巴是一种有用的血管扩张和体温调节的生物标志物，但在我们的实验中，只贡献了全身热量的5-8%，低于报告的大鼠的17%。在极端情况下，通过尾巴散热是重要的，例如棕色脂肪组织的药物激活；然而，在小鼠中，非尾巴对热量损失的贡献可能被低估了。

Body temperature is highly regulated in mammals. However, thermal biology in smaller mammals (such as mice) is different from that in larger mammals (such as adult humans). For example, when mice are singly housed at room temperature, about half of caloric intake is burned to maintain body temperature (referred to as cold-induced thermogenesis), while humans require little cold-induced thermogenesis. Upon fasting, mice can reduce their body temperature by >10 C, while humans with extreme starvation lower body temperature by only 0.2 C. We are exploring the use of body temperature as an indicator of the perceived metabolic status of the mouse. For example, what is the effect on body temperature of a genetic manipulation or drug treatment? What genetic manipulations or drug treatments cause dissociation of body temperature from nutritional status? What are the neurotransmitters and neural mechanisms involved? Mice are also an ideal model system to study hypothermia, as the central regulatory mechanisms are likely conserved across mammals, but the mice show much greater changes than larger mammals. Thus, mice are a more sensitive species that can suggest studies that might be productively undertaken in larger individuals such as adult humans. We are interested in the neural control of body temperature and hypothermia, and in understanding pharmacologic inducers of hypothermia. Progress in FY2021-22 includes the following: Understanding mouse thermal physiology informs the usefulness of mice as models of human disease. It is widely assumed that the mouse tail contributes greatly to heat loss (as it does in rat), but this has not been quantitated. We studied C57BL/6J mice after tail amputation. Tailless mice housed at 22 C did not differ from littermate controls in body weight, lean or fat content, or energy expenditure. With acute changes in ambient temperature from 19 to 39 C, tailless and control mice demonstrated similar body temperatures (Tb), metabolic rates, and heat conductances and no difference in thermoneutral point. Treatment with prazosin, an 1-adrenergic antagonist and vasodilator, increased tail temperature in control mice by up to 4.8 0.8 C. Comparing prazosin treatment in tailless and control mice suggested that the tails contribution to total heat loss was a non-significant 3.4 %. Major heat stress produced by treatment at 30 C with CL316243, a 3-adrenergic agonist, increased metabolic rate and Tb and at a matched increase in metabolic rate, the tailless mice showed a 0.72 0.14 C greater Tb increase and 7.6 % lower whole-body heat conductance. Thus, the mouse tail is a useful biomarker of vasodilation and thermoregulation, but in our experiments contributes only 5-8 % of whole-body heat dissipation, less than the 17 % reported for rat. Heat dissipation through the tail is important under extreme scenarios such as pharmacological activation of brown adipose tissue; however, non-tail contributions to heat loss may have been underestimated in the mouse.