fit基因特异性调控果蝇蛋白质进食行为的神经分子机制研究

Feeding behavior is the most basic biological process for organism healthy survival, which involves multiple regulations of nutrient homeostasis, endocrine system and nervous system. Different from carbohydrate and lipid, protein is most capable of causing satiety, resulting in inhibiting the further food intake.So far, the researches on feeding behavior regulation mostly focus on carbohydrate . The neural molecular mechanism of protein inhibiting food intake and which molecules play messenger roles between metabolic system and nervous system are still poorly understood. The applicant firstly discovered a protein specific sensing moleculer—fit (Female-specific Independent of Transformer) in preliminary work. As a Drosophila fat body secreted protein, Fit remotely control insulin secretion and is involved in protein intake behavior regulation. 3D reconstruction image displays fit expressed region is very closed to IPCs (Insulin-producing cells) neurons, which suggests the brain regions Fit may play a role in. This project aims to investigate the characteristics of fit expression, Fit targeting neurons, how Fit regulate insulin secretion, and the specific neural molecular mechanism involved in protein intake behavior. The research will significantly contribute to understand the neural regulation mechanisms from nutrient homeostasis to behavior control.

进食是生物体最重要的行为之一。有别于糖类和脂类，蛋白质食物最能够引起饱腹感，抑制下一步的进食。目前进食调控机制的探索多集中在糖类领域，蛋白质进食行为的研究方兴未艾，在营养内分泌组织和中枢神经系统间起到桥梁作用的生物分子更是未见报道。申请人在前期工作中首次发现了蛋白质特异性营养感知分子——fit (Female-specific Independent of Transformer)，其作为果蝇脂肪体分泌蛋白，跨组织调节胰岛素分子释放，特异性调控蛋白质进食行为，脑区三维重构暗示Fit可能作用于胰岛素分泌神经元 IPCs（Insulin Producing Cells）。本项目致力于揭示fit的表达调控特性、寻找Fit直接靶向神经元，研究其调控胰岛素释放的机制，探究fit特异性介导蛋白质进食行为的神经分子机理。本项目的研究成果对于揭示从营养内稳态到行为控制的跨系统信号调控通路具有重要意义。

进食是生物体最重要的行为之一，涉及到营养稳态平衡、内分泌系统和神经系统的多重调节和控制。目前进食调控机制的探索多集中在糖类领域，蛋白质进食行为的研究方兴未艾，在营养内分泌组织和中枢神经系统间起到桥梁作用的生物分子更是未见报道 。申请人在本项目中首次发现了蛋白质特异性营养感知分子——fit (Female-specific Independent of Transformer)，其作为果蝇脂肪体分泌蛋白，跨组织调节胰岛素分子释放，特异性调控蛋白质进食行为，脑区三维重构暗示Fit可能作用于胰岛素分泌神经元 IP Cs（Insulin Producing Cells）。并进一步揭示了fit的表达调控特性、寻找到了Fit直接 靶向神经元，研究其调控胰岛素释放的机制，探究fit特异性介导蛋白质进食行为的神经 分子机理。本项目的研究成果对于揭示从营养内稳态到行为控制的跨系统信号调控通路具 有重要意义。