Circadian Regulation of Neuropeptides from the Hypothalamus.

下丘脑神经肽的昼夜节律调节。

• 批准号: 203905-2012
• 负责人: Belsham, Denise
• 金额: $ 2.91万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=570013
• 关键词: Circadian; Regulation; Neuropeptides; Hypothalamus.

All organisms are continually subjected to a day/night cycle of approximately 24 hours. Through evolution, an internal biological clock developed as a means of anticipating this regular pattern. In mammals, the central or master biological clock is found in a small region of the brain, and is responsible for not only coordinating behaviour, but also the timing of basic physiological processes, such as arousal, cognition, hormonal regulation, metabolism and energy balance. This clock operates at the molecular level through a combination of positive and negative regulatory loops, involving transcription factors and other relevant proteins. These clock proteins are expressed in all cells, including the brain and other organs, such as the liver and the heart. At a basic level, a specific region of the brain called the hypothalamus, expresses a variety of neuropeptides that are directly responsible for the control of energy balance via a complex array of neuronal and hormonal signals. These hypothalamic signals lead to the initiation or cessation of feeding behaviour. Recently, the importance of the circadian system in weight regulation was validated when clock mutant mice, with an abnormal circadian cycle, were found to develop metabolic syndrome and obesity. We intend to study how the circadian machinery affects the rhythmic production of a number of specific proteins linked to feeding, and whether these rhythms can be affected by excess nutrient intake, such as sugars and fats, as is so common in obese states. Although it is generally accepted that the body operates quite routinely on a classic day/night schedule, the molecular events involved in the circadian regulation of basic physiological processes are not yet understood. Since the intact circadian clock is critical for maintaining metabolic processes, including energy balance in the body, we now intend to define the proteins that play a role in this process, and ultimately to identify the underlying regulatory mechanisms involved.

所有生物体都持续经历大约24小时的昼夜循环。 通过进化，内部生物钟发展成为预测这种规律的一种手段。在哺乳动物中，中央或主生物钟位于大脑的一个小区域，不仅负责协调行为，还负责基本生理过程的计时，例如觉醒、认知、激素调节、新陈代谢和能量平衡。这个时钟在分子水平上通过正调控环和负调控环的组合来运作，涉及转录因子和其他相关蛋白质。这些时钟蛋白在所有细胞中表达，包括大脑和其他器官，如肝脏和心脏。在基本水平上，大脑的一个特定区域称为下丘脑，表达各种神经肽，这些神经肽通过一系列复杂的神经元和激素信号直接负责控制能量平衡。这些下丘脑信号导致进食行为的开始或停止。最近，当发现具有异常昼夜节律周期的时钟突变小鼠发生代谢综合征和肥胖时，昼夜节律系统在体重调节中的重要性得到了验证。我们打算研究昼夜节律机制如何影响与进食相关的一些特定蛋白质的节律性产生，以及这些节律是否会受到过量营养素摄入的影响，如糖和脂肪，就像在肥胖状态下常见的那样。虽然人们普遍认为，身体的运作相当常规的一个经典的白天/黑夜的时间表，涉及的基本生理过程的昼夜节律调节的分子事件还没有被理解。由于完整的生物钟对于维持代谢过程（包括体内能量平衡）至关重要，我们现在打算定义在这一过程中发挥作用的蛋白质，并最终确定相关的潜在调控机制。