Circadian regulation of neuropeptides in the hypothalamus

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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.