What can body temperature tell us about energy homeostasis?

哺乳动物的体温受到高度调节。 然而，小型哺乳动物（如小鼠）的热生物学不同于大型哺乳动物（如成年人）。 例如，当小鼠单独在室温下饲养时，大约一半的热量摄入被燃烧以维持体温（兼性产热），而人类几乎不需要兼性产热。 在禁食时，小鼠可以将体温降低>10 ℃，而极度饥饿的人类只能将体温降低0.2 ℃。 我们正在探索使用体温作为小鼠感知代谢状态的指标。 例如，基因操作或药物治疗对体温有什么影响？ 什么基因操作或药物治疗导致体温与营养状况分离？ 涉及哪些神经递质和神经机制？ 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可能是保守的，但小鼠的变化比大型哺乳动物大得多。 因此，小鼠是一种更敏感的物种，可以建议在较大的个体（如成年人）中进行富有成效的研究。 我们感兴趣的是体温和体温过低的神经控制，并了解体温过低的药理学诱导剂。 二零一七财政年度的进展包括以下各项： 我们对先前的研究进行了随访，这些研究表明腺苷A3受体（A3AR）激动通过外周肥大细胞活化引起体温降低，引起组胺释放和中枢组胺1受体活化（1）。然后，我们发现A1AR激动剂起中枢作用，导致体温过低。 此外，我们发现，常用的A1AR激动剂药物也激动A3AR，并通过该机制引起体温降低，如果外周给药。 腺苷一磷酸（AMP）引起的体温降低不需要A1 AR和A3 AR。 A1AR和A3AR激动剂和AMP引起调节性体温过低，其特征在于总能量消耗下降、身体活动减少和偏好较冷的环境温度，表明体温设定点降低。A1AR和A3AR都不是禁食诱导的麻木所必需的。A1AR和A3AR激动剂和AMP触发剂通过三种不同的机制调节体温过低（2）。

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 (facultative thermogenesis), while humans require little facultative 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 FY2017 includes the following: We followed up on our prior studies showing that adenosine A3 receptor (A3AR) agonism causes hypothermia via peripheral mast cell activation, causing histamine release and activation of central histamine 1 receptors (1). We then showed that A1AR agonists acted centrally to cause hypothermia. In addition, we found that the commonly used A1AR agonist drugs were also agonizing A3AR and causing hypothermia via that mechanism, if given peripherally. The hypothermia causes by adenosine 5'-monophosphate (AMP) required neither A1AR nor A3AR. A1AR and A3AR agonists and AMP cause regulated hypothermia that was characterized by a drop in total energy expenditure, physical inactivity, and preference for cooler environmental temperatures, indicating a reduced body temperature set point. Neither A1AR nor A3AR was required for fasting-induced torpor. A1AR and A3AR agonists and AMP trigger regulated hypothermia via three distinct mechanisms (2).