Mobilization of Triacylglycerol Stores in Insects

昆虫体内三酰甘油储存的动员

• 批准号: 9133397
• 负责人: Estela L. Arrese
• 金额: $ 28.89万
• 依托单位: OKLAHOMA STATE UNIVERSITY STILLWATER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-02-01 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9133397
• 关键词: Acyltransferase; Adult; Aedes; Affect; Biology; Blood; Capsid Proteins; Cell physiology; Cells; Chemicals; Complex; Country; Culicidae; Cytoplasmic Organelle; Dengue; Deposition; Development; Diglycerides; Disease; Double-Stranded RNA; Drosophila genus; Energy Metabolism; Exhibits; Fat Body; Fatty Acids; Fatty acid glycerol esters; Female; Gene Silencing; Glycogen; Health; Hemolymph; Histocompatibility Testing; Hydrolysis; Individual; Insect Proteins; Insecta; Insecticide Resistance; Insecticides; Intervention; Investigation; Knowledge; Lead; Link; Lipase; Lipid Mobilization; Lipids; Lipolysis; Lipoproteins; Malaria; Manduca; Metabolic; Metabolic Pathway; Mosquito Control; Mosquito-borne infectious disease; Nutrient; Oocytes; Oogenesis; Organ; Ovary; Pathway interactions; Pharmaceutical Preparations; Phenotype; Phospholipids; Physiological; Play; Population; Process; Proteins; Public Health; RNA Interference; Regulation; Reproduction; Research Project Grants; Research Subjects; Role; Source; Staging; System; Tissues; Transferase; Transference; Triglycerides; Vaccines; base; diacylglycerol O-acyltransferase; egg; fatty acid metabolism; fitness; human disease; improved; innovation; lipid metabolism; lipid transfer protein; lipophorin; monolayer; particle; perilipin; prevent; protein expression; reproductive; vector control; vector mosquito

 DESCRIPTION (provided by applicant): Mosquitoes are vectors of a number of human diseases representing a serious problem for public health worldwide. Half of the world's population is exposed to malaria while dengue fever is a permanent threat in over 100 countries with 50-100 million individuals infected each year. To control mosquito-transmitted diseases, mosquito populations have been traditionally controlled by use of chemical insecticides. However, this approach is threatened by new mechanisms conferring insecticide resistance in mosquitoes. The lack of vaccines or drugs to prevent or cure mosquito transmitted diseases underscores the need to develop alternative strategies to control mosquito population. A detailed understanding of mosquito biology is a prerequisite for the development of new vector control strategies. In this context, we propose to study the mechanisms of storage and mobilization of fat stores in the vector mosquito, Aedes aegypti. The importance of energy reserves for reproduction is obvious in mosquitoes, such as the adult female A. aegypti. These females store low levels of nutrients, and they need a blood meal to acquire additional nutrients to complete the reproductive cycle. Following a blood meal, protein and lipid reserves are synthesized in the fat body and transported to the ovaries via hemolymph. Lipid reserves are transported by lipophorin (Lp). A salient feature of A. aegypti is that Lp carries TG. This feature separates mosquitoes from most insects in which Lp carries diacylglycerol (DG). In this project we propose to investigate key aspects of lipid mobilization in A. aegypti. The transference of TG to the ovaries is a complex process that starts with the hydrolysis of TG (lipolysis) stored in the fat body by the action of lipases. No lipase has been associated to this process in mosquito so far. This step is followed by re-synthesis of TG and loading to Lp by uncharacterized mechanisms. Our preliminary studies in A. aegypti identified a set of lipases, two acyl-transferases, and the Lipid Transfer Protein (LTP) as components of the mechanisms by which TG stored in lipid droplets are mobilized. Further, TG storage in the fat body of larval mosquito involves Lipid Droplet Storage protein 1 (Lsd1). In contrast, Lsd2 is more prominent in the fat body of vitellogenic A. aegypti females. As part of our continuing studies to understand the process of mobilization of TG stores in insects, we propose the following three aims: 1- To identify the main fat body lipases involved in the mobilization of fat body TG in A. aegypti; 2-To define the roles of lipid droplet-associated proteins AaLsd1 and AaLsd2 in the accumulation and mobilization of TG; 3- To investigate the role of acyl-transferases and LTP in the mechanism of synthesis and the secretion of TG in A. aegypti. Knowledge on the metabolism of lipids in this vector mosquito could be applied to improve our understanding of several physiological aspects, such as the regulation of oogenesis, mosquito fitness and survival. These are relevant aspects to the development of innovative strategies to control vector mosquito population.

 描述（由申请人提供）：蚊子是许多人类疾病的媒介，对全世界的公共卫生构成严重问题。世界上一半的人口受到疟疾的威胁，而登革热是100多个国家的永久性威胁，每年有5000万至1亿人感染。为了控制蚊子传播的疾病，传统上通过使用化学杀虫剂来控制蚊子种群。然而，这种方法受到蚊子对杀虫剂产生抗药性的新机制的威胁。由于缺乏预防或治疗蚊子传播疾病的疫苗或药物，因此需要制定替代战略来控制蚊子数量。详细了解蚊子生物学是制定新的病媒控制战略的先决条件。在这种情况下，我们建议研究的机制，储存和动员的脂肪储存在媒介蚊子，埃及伊蚊。能量储备对繁殖的重要性在蚊子中是显而易见的，例如成年雌性蚊子A。埃及人。这些雌性储存低水平的营养物质，它们需要血餐来获得额外的营养物质来完成生殖周期。血餐后，脂肪体内合成蛋白质和脂质储备，并通过血淋巴转运到卵巢。脂质储备由载脂蛋白（Lp）转运。A.埃及人是Lp携带TG。此功能 将蚊子与其中Lp携带二酰基甘油（DG）的大多数昆虫分开。在这个项目中，我们建议调查的关键方面，脂质动员在A。埃及人。TG向卵巢的转移是一个复杂的过程，始于储存在卵巢中的TG的水解（脂解）。 脂肪酶的作用使身体变胖。到目前为止，在蚊子中还没有脂肪酶与这一过程相关。该步骤之后是TG的再合成和通过未表征的机制加载到Lp。我们对A.埃及人鉴定了一组脂肪酶、两种酰基转移酶和脂质转移蛋白（LTP）作为储存在脂滴中的TG被动员的机制的组分。此外，蚊幼虫的脂肪体中的TG储存涉及脂滴储存蛋白1（Lsd 1）。相反，Lsd 2在卵黄发生A的脂肪体中更突出。埃及女性。作为我们继续研究的一部分，以了解动员的过程中TG商店在昆虫中，我们提出了以下三个目标：1-确定主要的脂肪体脂肪酶参与动员脂肪体TG在A。埃及人; 2.明确脂滴相关蛋白AaLsd 1和AaLsd 2在TG积累和动员中的作用; 3.研究脂滴相关蛋白AaLsd 1和AaLsd 2在A.埃及人。有关这种媒介蚊子脂质代谢的知识可以应用于提高我们对几个生理方面的理解，如卵子发生的调节，蚊子的健身和生存。这些都是与制定控制病媒蚊子种群的创新战略有关的方面。