What can body temperature tell us about energy homeostasis?

体温可以告诉我们关于能量稳态的什么信息？

• 批准号: 10248173
• 负责人: MARC L REITMAN
• 金额: $ 38万
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10248173
• 关键词: Acute; Adrenergic Agonists; Adrenergic Antagonists; Adult; Amputation; Biological Markers; Biological Models; Biology; Body Temperature; Body Weight; Brown Fat; Burn injury; Clinical; Dissociation; Energy Intake; Energy Metabolism; Fasting; Fatty acid glycerol esters; Heat Losses; Heat Stress Disorders; Homeostasis; House mice; Human; Individual; Injury; Link; Mammals; Metabolic; Mus; Neurotransmitters; Nutritional status; Pharmacology; Pharmacotherapy; Physiologic Thermoregulation; Physiological; Physiology; Prazosin; Rattus; Reporting; Starvation; Tail; Temperature; Thermogenesis; Thinness; Vasodilation; Vasodilator Agents; experimental study; genetic manipulation; human disease; human model; interest; metabolic rate; natural hypothermia; neuromechanism; neuroregulation

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 FY2020 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.

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（称为冷诱导产热），而人类几乎不需要冷诱导产热。 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。 二零二零财年的进展包括以下各项： 了解小鼠的热生理学告知小鼠作为人类疾病模型的有用性。人们普遍认为，小鼠的尾巴对热损失有很大的贡献（就像在大鼠中一样），但这还没有被量化。我们研究了断尾后的C57 BL/6 J小鼠。无尾小鼠在22 ℃下饲养与同窝对照小鼠在体重、瘦肉或脂肪含量或能量消耗方面没有差异。随着环境温度从19 ℃到39 ℃的急剧变化，无尾小鼠和对照小鼠表现出相似的体温（Tb）、代谢率和热导率，并且在热中性点上没有差异。用哌唑嗪（一种1-肾上腺素能拮抗剂和血管扩张剂）治疗，使对照小鼠的尾部温度升高至4.8 ± 0.8 ℃。在无尾小鼠和对照小鼠中比较哌唑嗪治疗表明，尾部对总热量损失的贡献为不显著的3.4%。在30 ℃下用CL 316243（β-肾上腺素能激动剂）处理产生的主要热应激增加了代谢率和Tb，并且在代谢率的匹配增加下，无尾小鼠显示出0.72 ± 0.14 ℃的更大Tb增加和7.6%的更低的全身热传导。因此，小鼠尾巴是血管舒张和体温调节的有用生物标志物，但在我们的实验中仅贡献全身散热的5- 8%，低于大鼠报告的17%。在极端情况下，通过尾部散热是重要的，例如棕色脂肪组织的药理学激活;然而，在小鼠中，非尾部对热量损失的贡献可能被低估了。