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

• 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
• 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

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.

这个实验室最近的研究提供了直接的证据，证明果蝇是一种合适的基因 研究进食行为控制和进食障碍的分子、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的苍蝇同源物，发挥着 在调节饥饿驱动的觅食和进食行为方面发挥重要作用。平行行为表型 在NPF缺陷果蝇和NPY基因敲除小鼠之间观察到：这两种动物在 基线摄食和体重控制，但在剥夺状态下表现出摄食不足；NPF缺乏 果蝇和NPY基因敲除小鼠对酒精镇静的敏感度也降低。最近， 我们已经获得了类似于哺乳动物胰岛素的证据，果蝇胰岛素样肽(DILPs) 通过作用于不同的神经元网络，包括NPY样神经元通路，抑制摄食反应。 例如，DILPs似乎通过类胰岛素直接抑制NPFR1神经元的信号活性。 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 调节觅食和取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。 这项拟议的研究旨在识别和表征更多的基因以及分子和神经元 饥饿驱动行为的关键途径。我们对基因和神经元特别感兴趣 对饥饿反应的不同方面进行不同的调控，如增强对食物的寻求，动机摄取 不太喜欢的食物，以及更高的摄入量。本申请的具体目的包括：1)分析 NPFR1神经元调节饥饿觅食的基因和分子途径；2) DILP对饥饿行为调控的基因和分子途径分析 3)功能增益筛选DILP/NPFR1神经元介导的饥饿反应的关键基因。 这些研究的结果可能会提供对遗传和神经因素如何影响人类健康的一般见解。 饥饿对包括哺乳动物在内的各种生物的食物反应的调节。