Satiety signaling in Caenorhabditis elegans

秀丽隐杆线虫的饱腹感信号传导

• 批准号: 7229989
• 负责人: Leon Avery
• 金额: $ 11.43万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7229989
• 关键词: Animals; Bacillus megaterium; Behavior; Behavioral Mechanisms; Bombesin; Caenorhabditis elegans; Candidate Disease Gene; Cholecystokinin; Condition; Consumption; Desire for food; Development; Eating; Exploratory Behavior; Family; Food; Gastrin releasing peptide; Genetic Screening; Glucagon; Goals; Homologous Gene; Hour; Human; Hunger; Hyperphagia; Knock-out; Learning; Locomotion; Mammals; Methods; Molecular; Motion; Movement; Mus; Mutation; Nematoda; Neuropeptide Receptor; Nutrient; Obesity; Obesity associated disease; Organ; Pathway interactions; Peptide YY; Protein Overexpression; Pump; RNA Interference; Rate; Satiation; Signal Pathway; Signal Transduction; Site; Somatostatin; Source; Starvation; Testing; Time; Transgenic Organisms; absorption; apolipoprotein A-IV; base; behavior influence; feeding; food quality; glucagon-like peptide 1; islet amyloid polypeptide; mutant; neuromedin B; peptide YY receptor; positional cloning; prevent; receptor; size

DESCRIPTION (provided by applicant): In humans, uncontrolled appetite and subsequent overeating cause obesity and obesity-associated diseases. Appetite is controlled in part by satiety signals that prevent the consumption of unneeded food. C. elegans may also be subject to satiety: feeding motions and exploratory behavior are reduced when worms are starved for 24 hours, then refed for 6 hours. This study aims to define C. elegans satiety signals that control appetite by identifying and characterizing the components of the pathway via a genetic screen. The hypotheses to be tested are (1) that worms induced to consume excess food become satiated, and (2) that satiety influences behavior via a specific molecular pathway or pathways. These hypotheses will be tested through 3 specific aims; Aim 1: Characterize the behavioral mechanisms of satiety. Subaim 1: Using insatiable mutations which are defective in feeding or nutrient absorption, we will determine whether reduction of feeding motions and locomotive activity in starved/refed worms are direct reflections of their satiety status. Subaim 2: Using different low and high-quality food sources, we will manipulate the conditions of satiety and examine whether feeding motions and.locomotive activity depend on food quality. Aim 2: Identify mutants that are defective in satiety behavior. Through genetic screening for mutants that have increased feeding motions and locomotive activity compared to wild type after starvation/refeeding, components of the satiety signaling pathway will be identified. Aim 3: Test candidate satiety signals. Cholecystokinin and peptide YY decrease meal size when exogenously administered to mice. We will target homologs of receptors for these neuropeptides by reverse genetic methods such as RNA interference. We will examine whether the knockout or overexpression of candidate receptors increases or decreases meal size

描述（由申请人提供）： 在人类中，不受控制的食欲和随后的暴饮暴食会导致肥胖和肥胖相关疾病。食欲部分是由饱腹感信号控制的，这些信号阻止了不需要食物的消费。秀丽隐杆线虫也可能会受到饱腹感的约束：当蠕虫饿死24小时时，喂食运动和探索行为会降低，然后再进行6小时。这项研究旨在通过遗传筛选来识别和表征途径的组成部分来定义秀丽隐杆线虫的饱腹感信号，以控制食欲。要测试的假设是（1）诱发食用多余食物的蠕虫被满足，并且（2）饱腹感通过特定的分子途径或途径影响行为。这些假设将通过3个特定目标进行检验；目标1：表征饱腹感的行为机制。 Subaim 1：使用在喂养或营养吸收中有缺陷的无限突变，我们将确定饥饿/ref的蠕虫中的进食运动和机车活性的减少是其饱腹感状态的直接反映。 Subaim 2：使用不同的低品质和高质量的食物来源，我们将操纵饱腹感的条件，并检查喂养运动和大量运动活性是否取决于食物质量。 AIM 2：确定饱腹部行为有缺陷的突变体。通过与饥饿/重新喂养后野生型相比，通过对饲喂运动和机车活性增加的突变体的基因筛查，将确定饱腹感信号通路的成分。 AIM 3：测试候选饱腹感信号。当外源给小鼠施用时，胆囊动蛋白和肽YY会降低粉状大小。我们将通过反向遗传方法（例如RNA干扰）靶向这些神经肽的受体同源物。我们将检查候选受体的敲除或过表达是否会增加或减小餐大小