果蝇脂肪体蛋白FIT对进食、睡眠行为的神经调控机制

营养感知通路涉及代谢、内分泌和神经等多个系统，其调控异常会引发肥胖、糖尿病等代谢疾患，也可能诱发嗜食症、失眠等神经性行为紊乱。因此，寻找将营养状态信号传递到大脑的关键信使因子，并探索其在神经系统中的下游信号通路和目标脑区，是揭开体内营养感知通路及其调控机体功能的重要途径和方法。申请人近年的工作鉴定出一个果蝇脂肪体蛋白FIT，其表达受体内氨基酸水平调控，突变体表现出进食、睡眠等行为异常，并参与中枢神经系统胰岛素信号的调控。本申请将系统研究FIT蛋白在营养信号向神经系统传递中的功能，及其调控进食、睡眠本能行为的神经分子机制，从神经生物学角度探索营养感知通路在行为调控和性别差异中的作用。此跨系统的整合研究将有助于理解代谢-内分泌-神经相关的综合性紊乱和疾病，并为诊断、干预及治疗方法提供理论依据。

Nutrition sensing pathway covers the metabolic, endocrine and nervous systems; malfunction of this pathway will trigger metabolic diseases or disorders like obesity and diabetes, may induce neuroethological disorders, like food addiction and insomnia. Thus, seeking for the key messenger factor that conveys the signal of nutritional status to the brain and studying its downstream signal pathways and target brain regions in the nervous system is an important approach to uncover the internal nutrition sensing pathway and its regulatory functions. The applicant’s recent work identified a fat body protein, Female-specific Independent of Transformer (FIT) in flies. Its expression is controlled by the internal amino acid state, and the knock-out mutant exhibits abnormal behaviors in food-intake and sleep; moreover, FIT is involved in the regulation of the insulin signaling in the central nervous system (CNS). This application will systemically investigate FIT function in delivering nutritional signals to the nervous system and the underlying molecular and neurobiological mechanisms in regulating innate behaviors like feeding and sleep, thereby exploring the regulatory function of nutrition sensing pathway on behavior control and its sexual dimorphism from the view of neurobiology. This cross-system integrated study will help to understand comprehensive disorders and diseases related to the metabolic, endocrine and nervous systems, and provide theoretical basis for diagnosis, interference and therapy.