Novel Central Actions of Thyroid Hormone in the Control of Body Temperature

甲状腺激素在体温控制中的新中枢作用

• 批准号: 445465132
• 负责人: Dr. Heiko Backes
• 金额: --
• 依托单位: Max-Planck-Institut für Stoffwechselforschung
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/445465132?language=en
• 关键词: Novel; Central; Actions; Thyroid; Hormone

Thyroid hormone is well known for its important role in body temperature regulation, as seen from the heat sensitivity of hyperthyroid patients. Recently, we were able to demonstrate in a mouse model that the hormone increases body temperature by eliciting hyperthermia in muscle in parallel with a central elevation of the body temperature set point as in fever/pyrexia. However, the precise neuroanatomical substrates by which thyroid hormone coordinates the thermogenic responses remain enigmatic.In this proposal we aim to identify novel sites of thyroid hormone action in the brain, which could mediate its effect on body temperature regulation. Using several different animal models with alterations in thyroid hormone signaling in combination with cutting edge technologies such as PET/CT or infrared thermography we will characterize the coordinated changes of thermoregulation with a special focus on brown fat thermogenesis. We thereby aim to dissect the crosstalk between the peripheral hyperthermia and the central pyrexia in correlation to brain activity. Our preliminary studies have already identified several brain regions that are activated by thyroid hormone, which we propose to be involved in body temperature regulation. We will test this hypothesis using stereotaxic delivery of thyroid hormone into the brain and aim to identify the precise neuronal populations using biochemical sorting and profiling of activated neurons.Our proposed project will provide a better understanding of how thyroid hormone controls body temperature and subsequently energy expenditure, which is of particular translational relevance for metabolic disorders such as obesity or type II diabetes.

众所周知，甲状腺激素在体温调节中的重要作用，从甲状腺功能亢进患者的热敏感性就可以看出。最近，我们能够在小鼠模型中证明，激素通过引起肌肉过热来提高体温，同时与发烧/发热时体温设定点的中心升高平行。然而，甲状腺激素协调产热反应的精确神经解剖学底物仍然是个谜。在这项提议中，我们的目标是确定大脑中甲状腺激素作用的新位点，这可以介导其对体温调节的影响。使用几种不同的甲状腺激素信号改变的动物模型，结合 PET/CT 或红外热成像等尖端技术，我们将描述温度调节的协调变化，特别关注棕色脂肪的生热作用。因此，我们的目标是剖析与大脑活动相关的外周发热和中枢发热之间的串扰。我们的初步研究已经确定了几个被甲状腺激素激活的大脑区域，我们认为这些区域与体温调节有关。我们将通过立体定位将甲状腺激素输送到大脑中来测试这一假设，并旨在通过激活神经元的生化分类和分析来识别精确的神经元群。我们提出的项目将更好地理解甲状腺激素如何控制体温和随后的能量消耗，这对于肥胖或 II 型糖尿病等代谢性疾病具有特殊的转化相关性。