Drosophila feeding behavior: New tools for the genetic dissection of prandiology

描述(申请人提供)：不正常的进食行为定义了人类的疾病，如厌食症和暴食症，并可能导致慢性疾病的发展。例如，肥胖可能是食物摄入量和能量消耗之间的不平衡造成的，并与糖尿病和心血管疾病的发病率增加以及生活质量下降、医疗费用增加和过早死亡有关。更好地了解食欲调节将导致更好的控制食物摄入量的方法，从而更好地治疗与食物相关的疾病。果蝇，黑腹果蝇，是研究基因与行为和疾病关系的强大系统。由于缺乏测量苍蝇食物消耗的精确工具，对饥饿、饱腹感和进餐时间的分析一直被忽视，尽管饮食习惯在肥胖、高胆固醇血症和糖尿病的生理病理中可能发挥了作用。该项目的目标是1)开发测量苍蝇短期和长期食物消耗的简单工具，以及2)识别和表征具有异常摄食行为的基因突变。这项工作将显著提高该领域的能力，并导致肥胖、摄食和成瘾苍蝇模型的广泛使用和发展。苍蝇如何做出以食物为基础的决定将为人类行为的研究提供信息，并将在遗传和神经元水平上更好地理解构成食欲和进食行为的核心机制。这些发现对于开发新的治疗方法以及肥胖和其他疾病的预防措施至关重要。 公共卫生相关性：肥胖、厌食症和暴食症等进食和代谢障碍会导致糖尿病、中风和心血管疾病--极大地降低生活质量并增加医疗费用。果蝇是一种果蝇，几十年来一直被用作了解哺乳动物疾病的强大遗传模型，但由于目前可用的技术较差，它在研究摄食和食欲方面的应用一直受到限制。该项目将1)开发一个测量个体苍蝇摄食量的自动化系统，2)识别控制摄食行为的基因，以建立无脊椎动物和哺乳动物模型系统之间的相似之处。

DESCRIPTION (provided by applicant): Abnormal feeding behaviors define human disorders such as anorexia and bulimia, and can lead to the development of chronic disease. Obesity, for example, can result from an imbalance between food intake and energy expenditure, and is associated with increased incidence of diabetes and cardiovascular disease, as well as with reduced quality of life, increased healthcare costs, and premature death. A better understanding of appetite regulation will lead to better methods for controlling food intake, and therefore to better treatments for food-related disorders. The fruit fly, Drosophila melanogaster, is a powerful system for studying the relationship of genes with behavior and disease. Because of the lack of precise tools for measuring fly food consumption, the analysis of hunger, satiety, and the timing of meals has been neglected, despite the possible role played by prandial habits in the physiopathology of obesity, hypercholesterolemia, and diabetes. The goals of this project are to 1) develop simple tools for measuring short- and long-term food consumption in flies and 2) identify and characterize genetic mutants with abnormal feeding behavior. This work will significantly enhance the capabilities of the field and result in expanded use and development of fly models of obesity, feeding, and addiction. How flies make food-based decisions will inform studies on human behavior, and will provide a better understanding of the central mechanisms that underlie appetite and feeding behavior at the genetic and neuronal levels. These discoveries are vital to the development of new therapeutics as well as preventative measures for obesity and other diseases. PUBLIC HEALTH RELEVANCE: Feeding and metabolic disorders such as obesity, anorexia, and bulimia contribute to diabetes, stroke, and cardiovascular disease-greatly reducing quality of life and increasing health care costs. Drosophila, the fruit fly, has been used for decades as a powerful genetic model for understanding mammalian disease, but its use in studying feeding and appetite has been limited due to the poor techniques currently available. This project will 1) develop an automated system for measuring consumption from individual flies and 2) identify genes that regulate feeding behavior to establish parallels between invertebrate and mammalian model systems.