Satiety signaling in Caenorhabditis elegans

秀丽隐杆线虫的饱腹感信号传导

• 批准号: 7036421
• 负责人: Leon Avery
• 金额: $ 11.78万
• 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 2007-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7036421
• 关键词: Caenorhabditis elegans; RNA interference; appetite; behavior test; behavioral /social science research tag; behavioral genetics; biological signal transduction; cholecystokinin; eating disorders; gene mutation; genetic screening; genetically modified animals; helminth genetics; invertebrate locomotion; malnutrition; nutrient intake activity; nutrition related tag; satiations

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。食欲在一定程度上是由饱腹感信号控制的，饱腹感信号可以防止消耗不需要的食物。线虫也可能会产生饱腹感：当线虫饥饿 24 小时，然后再进食 6 小时时，进食动作和探索行为会减少。本研究旨在通过遗传筛选识别和表征该途径的组成部分，从而定义控制食欲的线虫饱腹感信号。要测试的假设是（1）诱导消耗过量食物的蠕虫变得饱足，以及（2）饱足感通过特定的分子途径影响行为。这些假设将通过 3 个具体目标进行检验；目标 1：描述饱腹感的行为机制。 Subaim 1：利用摄食或营养吸收方面有缺陷的贪得无厌突变，我们将确定饥饿/进食蠕虫中摄食运动和运动活动的减少是否是其饱腹感状态的直接反映。 Subaim 2：使用不同的低质量和高质量食物来源，我们将操纵饱腹感的条件并检查进食动作和运动活动是否取决于食物质量。目标 2：识别在饱腹感行为方面存在缺陷的突变体。通过对饥饿/再喂养后与野生型相比增加进食运动和运动活性的突变体进行遗传筛选，将鉴定饱足感信号通路的组成部分。目标 3：测试候选者的饱腹感信号。当对小鼠进行外源性给药时，胆囊收缩素和肽 YY 会减少膳食量。我们将通过RNA干扰等反向遗传方法来靶向这些神经肽受体的同源物。我们将检查候选受体的敲除或过度表达是否会增加或减少膳食量