Roles of Drosophila NPY-and Insulin-like Activities in Food Response

果蝇 NPY 和类胰岛素活性在食物反应中的作用

基本信息

批准号：
7804629
负责人：
PING SHEN
金额：
$ 25.41万
依托单位：
UNIVERSITY OF GEORGIA
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-05-01 至 2014-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7804629
关键词：
Acute Animals Behavior Behavior Control Behavioral Biological Assay Body Weight Cells Collection Critical Pathways Dominant-Negative Mutation Double-Stranded RNA Drosophila genus Drosophila neuropeptide F Eating Disorders Fasting Feeding behaviors Food Food Preferences Food deprivation (experimental)Genes Genetic Genetic Models Genome Genomics Goals Homologous Gene Humulus Hunger Ingestion Insulin Intake Knockout Mice Laboratory Research Larva Lesion Mammals Mediating Modeling Molecular Neurons Organism Pathway interactions Peptide Synthesis Peptides Phenotype Play Proteins RNA Interference Regulation Research Research Personnel Ribosomal Protein S6 Kinase Role Sedation procedure Signal Pathway Signal Transduction Signaling Molecule Stimulus Structure-Activity Relationship System Testing Transgenic Organisms Weight maintenance regimen alcohol sensitivity base design driving behavior feeding fly food quality gain of function gene replacement insight insulin signaling interest loss of function mutant neuromechanism neuropeptide F neuropeptide Y novel overexpression promoter receptor relating to nervous system response vector

项目摘要

The recent research from this laboratory provides direct evidencethat Drosophila is a suitable genetic model for studying molecular, cellular and neural basis of feeding behavioral control and eating disorders. We have shown that Drosophila neuropeptide F (NPF), the fly homologue of mammalian NPY, plays an important role in regulating hunger-driven foraging and feeding behaviors. Parallel behavioral phenotypes have been observed between NPF-deficient flies and NPY-knockoutmice: both animals were normal in baseline feeding and body weight control but displayed feeding deficits in the deprived state; NPF-deficient flies and NPY knockout mice also displayed decreased acute sensitivity to ethanol sedation. More recently, we have obtained evidence that analogous to mammalian insulin, Drosophila insulin-like peptides (DILPs) suppress feeding response by acting oh different neuronal networks including the NPY-like neuronal pathway. For example, DILPs appear to directly inhibit the signaling activity of NPFR1 neurons through the insulin-like receptor (lnR)/ribosomal S6 kinase (S6K) pathway. Taken together, our findings strongly suggest that signaling mechanisms for the regulation of foraging and feeding behaviors are largely conservedbetween flies and mammals. The proposed research aims to identify and characterize additional genes and molecular and neuronal pathways critical for hunger-driven behaviors. We are particularly interested in genes and neurons that differentially regulate distinct aspects of hunger response such as enhanced food seeking, motivated intake of less-preferred foods, and increased ingestion rate. The specific aims of this application include: 1) Analysis of genes and molecular pathways underlying the regulation of hunger-motivated foraging by NPFR1 neurons; 2) Analysis of genes and molecular pathways underlying the regulation of hunger-driven behaviors by DILP neurons; 3) Gain-of-function screen for genes critical for DILP/NPFR1 neuron-mediated hunger response. The results from these studies may provide general insights into how genetic and neural factors contribute to hunger regulation of food response in diverse organisms including mammals.

该实验室最近的研究提供了直接证据表明果蝇是合适的遗传基因研究喂养行为控制和饮食失调的分子、细胞和神经基础的模型。我们已经证明，果蝇神经肽 F (NPF)（哺乳动物 NPY 的果蝇同源物）发挥着在调节饥饿驱动的觅食和进食行为方面发挥着重要作用。平行行为表型在 NPF 缺陷果蝇和 NPY 敲除小鼠之间观察到：两种动物的基线喂养和体重控制，但在剥夺状态下表现出喂养不足； NPF缺乏果蝇和 NPY 敲除小鼠也表现出对乙醇镇静的急性敏感性降低。最近，我们已经获得证据表明，果蝇胰岛素样肽（DILP）与哺乳动物胰岛素类似通过作用于不同的神经元网络（包括 NPY 样神经元通路）来抑制进食反应。例如，DILPs 似乎可以通过类胰岛素直接抑制 NPFR1 神经元的信号传导活性。受体 (lnR)/核糖体 S6 激酶 (S6K) 途径。综上所述，我们的研究结果强烈表明调节觅食和摄食行为的信号机制在很大程度上是保守的苍蝇和哺乳动物。拟议的研究旨在识别和表征其他基因以及分子和神经元对饥饿驱动行为至关重要的途径。我们对基因和神经元特别感兴趣差异化地调节饥饿反应的不同方面，例如增强食物寻找、主动摄入不太喜欢的食物，并增加摄入率。该应用程序的具体目标包括： 1) 分析 NPFR1 神经元调节饥饿动机觅食的基因和分子途径； 2） DILP 调节饥饿驱动行为的基因和分子途径分析神经元； 3) 对 DILP/NPFR1 神经元介导的饥饿反应至关重要的基因的功能获得筛选。这些研究的结果可能提供关于遗传和神经因素如何影响的一般见解。包括哺乳动物在内的多种生物体的食物反应的饥饿调节。