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.

体温在哺乳动物中受到高度调节。 但是，较小的哺乳动物（例如小鼠）中的热生物学与较大的哺乳动物（例如成年人）的热生物学不同。 例如，当小鼠在室温下单独容纳小鼠时，大约一半的热量摄入量以保持体温（称为冷诱导的热发生），而人类几乎不需要冷诱导的热生成。 禁食后，小鼠可以将其体温降低> 10 c，而极端饥饿的人类仅降低体温为0.2 C。 我们正在探索体温用作小鼠感知的代谢状态的指标。 例如，对遗传操作或药物治疗的体温有什么影响？ 哪些遗传操作或药物治疗导致体温与营养状况解离？ 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，因为中央调节机制可能是在哺乳动物中保守的，但是小鼠比较大的哺乳动物显示出更大的变化。 因此，小鼠是一种更敏感的物种，可以提出可能在诸如成年人之类的大个子中进行有效进行的研究。 我们对体温和体温过低的神经控制感兴趣，以及了解体温过低的药理学诱导剂。 FY2021-22中的进展包括以下内容： 了解小鼠热生理学将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），但尚未进行定量。尾截肢后我们研究了C57BL/6J小鼠。容纳22 C的尾鼠小鼠与体重，瘦含量或脂肪含量或能量消耗的同窝对照没有差异。随着环境温度从19至39 C的急性变化，尾鼠和对照小鼠表现出相似的体温（TB），代谢率和热电导率，并且热肾上腺点没有差异。 1-肾上腺素能拮抗剂和血管扩张剂帕索辛治疗对照小鼠中的尾部温度提高了4.8 0.8 C.比较尾鼠和对照小鼠的prazosin处理表明，尾巴对总热量损失的贡献是无显着的3.4％。 30 c治疗在30 c治疗中，CL316243是一种3-肾上腺素激动剂，代谢率和结核病增加，代谢率增加时，尾鼠的小鼠显示出0.72 0.14 c TB的增加，增加了7.6％的全身热电导率。因此，小鼠尾巴是血管舒张和温度调节的有用生物标志物，但是在我们的实验中，仅贡献了全身散热的5-8％，小于报告的17％的大鼠。在极端情况下，诸如棕色脂肪组织的药理激活之类的极端情况下，通过尾巴的热量耗散很重要。但是，在小鼠中可能低估了对热量损失的非尾贡献。