Regulation of long term feeding and triglyceride storage using Drosophila

利用果蝇调节长期饲养和甘油三酯储存

• 批准号: 7140672
• 负责人: Pankaj Kapahi
• 金额: $ 23.68万
• 依托单位: BUCK INSTITUTE FOR RESEARCH ON AGING
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-30 至 2007-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7140672
• 关键词: Drosophilidae; adenine nucleotides; appetite; arthropod genetics; behavioral /social science research tag; behavioral genetics; bioenergetics; body physical activity; dietary carbohydrates; dietary lipid; dietary proteins; disease /disorder model; fungal proteins; genetic strain; genetic susceptibility; glucose; lipid metabolism; nutrition related tag; obesity; overeating; respiratory oxygen; site directed mutagenesis; triglycerides

DESCRIPTION (provided by applicant): We propose to study the genetic basis of obesity using Drosophila. Obesity results from a greater energy intake than energy expenditure. Hence, the modification of eating behavior seems essential to avert the obesity crisis. We seek to identify dysregulation in metabolic feedback regulation leading to overeating in Drosophila. Excess nutrients are stored as triglycerides during obesity. We have observed that nutrient quality can modulate triglyceride storage in Drosophila. We propose to study the genetic basis for how nutrient quality can cause changes in triglyceride storage. Firstly, we propose to identify and characterize genes that regulate the long-term feeding rate of carbohydrates in Drosophila, which have been shown to possess such regulatory mechanisms. We have developed a rapid screening method, to identify strains that fail to inhibit feeding behavior after prolonged exposure to a diet containing excess carbohydrates. Using P element mediated mutagenesis we shall identify genes that regulate long term feeding behavior in Drosophila. From a pilot screen of 200 strains we have isolated two strains that fail to show a reduced inhibition of feeding rate in spite of being fed a diet rich in carbohydrates. The isolated mutants will be characterized for their energy status, mortality rate, physical activity, metabolic rate and respiratory quotient to give us better insight into the link between food intake and metabolism. Secondly, we aim to identify and characterize genes that regulate triglyceride storage. As part of our study, we shall examine dietary manipulations that recapitulate the "Atkins effect". A protein-rich, carbohydrate-poor diet, which is claimed to help lose fat in humans, also reduces fat in Drosophila. We aim to uncover the genetic basis for the reduction of fat on a diet that is rich in protein source using Drosophila. We propose to screen for regulators of triglyceride storage upon varying protein source (yeast extract) in the fly using P element mediated mutagenesis. Drosophila display long-term regulation of feeding behavior and obesity phenotypes like humans. The advanced genetic tools, the speed of discovery, and the complex nervous system of Drosophila make it an excellent choice as a model organism for examining causes of obesity. Given the high degree of genetic homology between humans and flies, we believe it is timely to examine the genetic causes of obesity in Drosophila. Our findings will significantly affect our understanding of the causes of obesity, which is a growing epidemic in the world.

描述（由申请人提供）： 我们建议使用果蝇研究肥胖的遗传基础。肥胖是由于能量摄入量要比能量消耗更大的产生。因此，饮食行为的修改似乎对于避免肥胖危机至关重要。我们试图确定代谢反馈调节的失调，导致果蝇暴饮暴食。肥胖期间，多余的营养成分作为甘油三酸酯。我们已经观察到，营养质量可以调节果蝇中的甘油三酸酯储存。我们建议研究营养质量如何导致甘油三酸酯储存变化的遗传基础。 首先，我们建议识别和表征调节果蝇中碳水化合物长期进食率的基因，这些基因已被证明具有这种调节机制。我们已经开发了一种快速筛选方法，以确定长期暴露于含有过量碳水化合物的饮食后无法抑制喂养行为的菌株。使用P元素介导的诱变，我们应确定调节果蝇长期喂养行为的基因。从200个菌株的试验屏幕中，我们分离了两种菌株，尽管饮食中富含碳水化合物的饮食，但未能显示出降低的喂养速率的抑制作用。孤立的突变体的特征是其能量状况，死亡率，体育锻炼，代谢率和呼吸商，以使我们可以更好地了解食物摄入与代谢之间的联系。 其次，我们旨在识别和表征调节甘油三酸酯储存的基因。作为研究的一部分，我们将检查饮食中概括“阿特金斯效应”的饮食操纵。一种富含蛋白质的碳水化合物饮食，据称可以帮助人类减少脂肪，还可以减少果蝇的脂肪。我们旨在发现使用果蝇富含蛋白质来源的脂肪减少脂肪的遗传基础。我们建议使用P元素介导的诱变在不同的蛋白质源（酵母提取物）中筛选甘油三酸酯存储的调节剂。 果蝇表现出对喂养行为和肥胖表型的长期调节。先进的遗传工具，发现速度和果蝇的复杂神经系统使其成为检查肥胖原因的模型生物的绝佳选择。鉴于人与苍蝇之间的遗传同源性高度，我们认为及时检查果蝇肥胖的遗传原因。我们的发现将严重影响我们对肥胖原因的理解，这是世界上日益增长的流行病。