Circadian Regulation of Neuropeptides from the Hypothalamus.

所有生物体都会持续经历大约24小时的昼夜循环。通过进化，形成了一种内在的生物钟，作为预测这种规律的手段。在哺乳动物中，中央生物钟或主生物钟位于大脑的一小块区域，不仅负责协调行为，还负责基本生理过程的时间安排，如唤醒、认知、激素调节、新陈代谢和能量平衡。这个时钟通过正负调控环的组合在分子水平上运作，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都有表达，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摄食行为的开始或停止。最近，当昼夜节律异常的时钟突变小鼠被发现发展为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摄食有关的一些特定蛋白质的节律产生，以及这些节律是否会受到过量营养摄入的影响，例如糖和脂肪，就像肥胖状态中常见的那样。虽然人们普遍认为人体按典型的昼夜节律运转，但基本生理过程的昼夜节律所涉及的分子事件尚不清楚。由于完整的生物钟对维持新陈代谢过程至关重要，包括体内的能量平衡，我们现在打算定义在这一过程中发挥作用的蛋白质，并最终确定涉及的潜在调控机制。

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 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.