Obesity and regulation of energy homeostasis in Drosophila melanogaster

果蝇的肥胖与能量稳态调节

• 批准号: 7362382
• 负责人: Tania Reis
• 金额: $ 4.88万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7362382
• 关键词: Address; Affect; Animal Feed; Animals; Behavior; Behavioral; Biological; Biological Assay; Biological Models; Body fat; Brain; Brain Part; Brain region; Caloric Restriction; Carbohydrates; Communication; Complex; Condition; Consumption; Depth; Diabetes Mellitus; Diet; Diet Monitoring; Disease; Disruption; Distant; Drosophila genus; Drosophila melanogaster; Eating; Energy Intake; Energy Metabolism; Engineering; Equilibrium; Expenditure; Fat Body; Fatty acid glycerol esters; Feeding behaviors; Fertility; Food; Food Energy; Food Processing; Gene Activation; Gene-Modified; Genes; Genetic; Genetic Screening; Genome; Glycogen; Growth and Development function; Health; Heart Diseases; Homeostasis; Human; Incidence; Intake; Knowledge; Laboratory mice; Larva; Lipids; Longevity; Malignant Neoplasms; Measures; Molecular; Molecular Genetics; Nervous system structure; Neuraxis; Neurons; Nutritional; Obesity; Organ; Organism; Pathway interactions; Physiological; Play; Prevention; Protein Overexpression; Proteins; Range; Rate; Regulation; Regulatory Pathway; Research; Resources; Role; Satiation; Sense Organs; Sensory; Source; System; Tissues; Transgenic Organisms; Trehalose; Triglycerides; Vesicle; energy balance; feeding; fly; food consumption; gain of function; genetic manipulation; improved; mind control; mutant; novel; nutrition; research study; response; sugar; tool; tumor

DESCRIPTION (provided by applicant): Obesity is a complex disorder resulting from misregulation of specific biological pathways controlling the balance between energy consumption and expenditure, and is associated with health problems ranging from heart disease and diabetes to several kinds of cancer. Conversely, caloric restriction has been shown to result in a reduction of incidence of spontaneous tumors in laboratory mice. However, it is clear that obesity is not simply an effect of excessive food intake. Significant progress has been made towards identifying pathways involved in obesity, but a deeper understanding of the disease is required in order to meet the growing demand for effective treatments. The field of obesity research is in need of an experimental system that can combine amenability to genetic manipulation with some of the physiological complexity of humans. The proposed research will develop Drosophila melanogaster as a model system to identify new pathways controlling energy homeostasis. Flies offer extensive genetic tools and the physiological complexity required for these studies, as they possess sensory, circulatory and storage organs. Maintaining energy balance requires coordination of the nervous system (sensing satiety and regulating behavior) and energy storage tissues (storing energy as fat/sugar or mobilizing it). The proposed studies will determine the effects of modified diets on the types and levels of energy storage, and identify pathways comprising the regulatory network for energy homeostasis, including which organs sense and process food sources and physiological changes in energy levels. Specifically, these experiments aim to: (1) determine the effects of diet on the balance between intake (amount/type of food consumed) and usage (amount/type of energy stored); (2) address the role of the nervous system in regulating overall physiological energy balance and identify which specific regions of the brain are involved; and (3) identify inter-organ communication pathways responsible for maintaining the organism energy balance. Developing fruit flies will be fed modified diets and effects on levels of fat and other forms of energy storage, rates of food consumption, and overall growth and development will be assessed. To identify regions of the brain required for normal energy balance, genetically engineered flies will be used to ablate the function of specific groups of neurons and determine the effects on levels of fat stored and food ingested. Finally, a genome-wide screen will be performed to identify genes modifying fat storage and/or rates of food consumption. Knowledge of the diets and physiological conditions prone to inducing obesity will improve our understanding of this disorder and identify potential targets for both its treatment and prevention.

描述（由申请人提供）：肥胖是一种复杂的疾病，由控制能量消耗和消耗之间平衡的特定生物途径失调引起，与心脏病、糖尿病和几种癌症等健康问题有关。相反，热量限制已被证明可以减少实验室小鼠自发性肿瘤的发生率。然而，很明显，肥胖不仅仅是食物摄入过多的结果。在确定与肥胖有关的途径方面已经取得了重大进展，但为了满足对有效治疗日益增长的需求，还需要对这种疾病有更深入的了解。肥胖研究领域需要一种实验系统，能够将基因操纵的适应性与人类的一些生理复杂性结合起来。