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: 10697821
• 负责人: MARC L REITMAN
• 金额: $ 40.63万
• 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/10697821
• 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 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.

哺乳动物的体温受到高度调节。 然而，小型哺乳动物（如小鼠）的热生物学与大型哺乳动物（如成年人）不同。 例如，当小鼠单独饲养在室温下时，大约一半的热量摄入被燃烧以维持体温（称为冷诱导生热），而人类几乎不需要冷诱导生热。 禁食后，小鼠的体温可降低>10℃，而极度饥饿的人类体温仅降低0.2℃。 我们正在探索使用体温作为小鼠代谢状态感知的指标。 例如，基因操纵或药物治疗对体温有何影响？ 哪些基因操作或药物治疗会导致体温与营养状况脱节？ 涉及哪些神经递质和神经机制？ 小鼠也是研究低温的理想模型系统，因为哺乳动物的中央调节机制可能是保守的，但小鼠比大型哺乳动物表现出更大的变化。 因此，小鼠是一种更敏感的物种，可以建议在较大个体（例如成年人）中进行有效的研究。 我们对体温和体温过低的神经控制以及了解体温过低的药理学诱导剂感兴趣。 2021-22 财年的进展包括： 了解小鼠热生理学可以了解小鼠作为人类疾病模型的有用性。人们普遍认为，小鼠尾巴对热量损失有很大贡献（就像在大鼠中一样），但这尚未得到量化。我们研究了断尾后的 C57BL/6J 小鼠。饲养在 22°C 环境下的无尾小鼠在体重、瘦肉或脂肪含量或能量消耗方面与同窝对照小鼠没有差异。当环境温度从 19°C 急剧变化到 39°C 时，无尾小鼠和对照小鼠表现出相似的体温 (Tb)、代谢率和热导，并且热中性点没有差异。使用哌唑嗪（一种 1-肾上腺素能拮抗剂和血管扩张剂）治疗，对照小鼠的尾部温度升高了 4.8±0.8℃。比较无尾小鼠和对照小鼠的哌唑嗪治疗表明，尾部对总热量损失的贡献并不显着，为 3.4%。在 30°C 下用 3-肾上腺素能激动剂 CL316243 治疗产生的主要热应激，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°C，全身降低了 7.6%热导率。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%，低于报道的大鼠的 17%。在极端情况下，例如棕色脂肪组织的药理激活，通过尾部散热非常重要；然而，在小鼠中，非尾部对热量损失的贡献可能被低估了。