Circadian regulation of neuropeptides in the hypothalamus

所有生物都持续地经历大约24小时的昼夜循环。通过进化，一个内部生物钟发展成为预测这种规律模式的手段。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定时，如觉醒、认知、激素调节、代谢和能量平衡。这个时钟在分子水平上通过正负调节环的组合来运作，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。在基本层面上，大脑中有一个叫做下丘脑的特定区域，通过一系列复杂的神经元和激素信号，表达各种神经肽，这些神经肽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，昼夜节律系统在体重调节中的重要性被证实，生物钟突变小鼠，昼夜节律周期异常，被发现发展代谢综合征和肥胖。我们打算研究昼夜节律机制如何影响与进食相关的四种特定蛋白质的节律性产生，以及这些节律是否会受到中央生物钟神经元产生的输出信号的影响。尽管人们普遍认为身体的运作是按照经典的昼夜节律进行的，但涉及基本生理过程的昼夜节律调节的分子事件尚未被理解。由于完整的生物钟对于维持代谢过程至关重要，包括体内的能量平衡，我们现在打算确定在这一过程中发挥作用的蛋白质，并最终确定所涉及的潜在调节机制。

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 four specific proteins linked to feeding, and whether these rhythms can be affected from output signals produced by neurons in the central biological clock. 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.