Obesity and regulation of energy homeostasis in Drosophila melanogaster

果蝇的肥胖与能量稳态调节

• 批准号: 7220394
• 负责人: Tania Reis
• 金额: $ 4.6万
• 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/7220394
• 关键词: Drosophilidae; bioenergetics; biological signal transduction; brain mapping; experimental brain lesion; fertility; gene induction /repression; genetic regulation; genetic screening; growth /development; larva; lipid biosynthesis; longevity; mutant; neuroregulation; nutrition; nutrition related tag; obesity; postdoctoral investigator; trehalose; triglycerides; vesicle /vacuole

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）：肥胖是由控制能量消耗和支出之间的平衡的特定生物途径的失调引起的复杂病症，并且与从心脏病和糖尿病到几种癌症的健康问题相关。相反，热量限制已被证明会导致实验室小鼠自发性肿瘤的发生率降低。然而，很明显，肥胖不仅仅是食物摄入过量的结果。在确定肥胖症相关途径方面已经取得了重大进展，但需要对该疾病有更深入的了解，以满足对有效治疗日益增长的需求。肥胖研究领域需要一种实验系统，可以将对遗传操作的顺从性与人类的一些生理复杂性结合起来。 这项拟议的研究将开发果蝇作为一个模型系统，以确定控制能量稳态的新途径。苍蝇提供了广泛的遗传工具和这些研究所需的生理复杂性，因为它们拥有感觉，循环和储存器官。 维持能量平衡需要神经系统的协调（感知饱腹感和调节 行为）和能量储存组织（将能量储存为脂肪/糖或动员它）。拟议的研究将确定改良饮食对能量储存类型和水平的影响，并确定构成能量稳态调节网络的途径，包括哪些器官感知和处理食物来源以及能量水平的生理变化。具体而言，这些实验旨在：（1）确定饮食对摄入量之间平衡的影响（食物消耗量/种类）和使用（2）解决神经系统在调节整体生理能量平衡中的作用，并确定大脑的哪些特定区域参与其中;以及（3）识别负责维持生物体能量平衡的器官间通信途径。发育中的果蝇将被喂食改良的饮食，并将评估对脂肪水平和其他形式的能量储存、食物消耗率以及整体生长和发育的影响。为了确定正常能量平衡所需的大脑区域，基因工程果蝇将被用来消除特定神经元群的功能，并确定对储存的脂肪和摄入的食物水平的影响。最后，将进行全基因组筛选，以确定改变脂肪储存和/或食物消耗率的基因。了解容易诱发肥胖的饮食和生理条件将提高我们对这种疾病的理解，并确定其治疗和预防的潜在目标。