Mobilization of Triacylglycerol Stores in Insects

昆虫体内三酰甘油储存的动员

• 批准号: 9306148
• 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/9306148
• 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; Hemolymph; Hydrolysis; Hydrophobicity; 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; 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; public health relevance; 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）：蚊子是多种人类疾病的媒介，这些疾病对全世界的公共卫生构成严重问题。世界上一半的人口感染疟疾，而登革热对 100 多个国家构成永久威胁，每年有 50-1 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数量。然而，这种方法受到赋予蚊子杀虫剂抗药性的新机制的威胁。缺乏预防或治疗蚊子传播疾病的疫苗或药物强调需要制定替代策略来控制蚊子数量。详细了解蚊子生物学是制定新的病媒控制策略的先决条件。在这种背景下，我们建议研究媒介蚊子埃及伊蚊的脂肪储存和动员机制。能量储备对繁殖的重要性对于蚊子来说是显而易见的，例如成年雌性埃及伊蚊。这些雌性储存的营养水平较低，它们需要血粉来获取额外的营养来完成生殖周期。吸血后，蛋白质和脂质储备在脂肪体内合成，并通过血淋巴输送到卵巢。脂质储备由脂蛋白 (Lp) 运输。埃及伊蚊的一个显着特征是Lp携带TG。此功能 将蚊子与大多数 Lp 携带二酰基甘油 (DG) 的昆虫区分开来。在这个项目中，我们建议研究埃及伊蚊脂质动员的关键方面。 TG 转移到卵巢是一个复杂的过程，首先是储存在卵巢中的 TG 水解（脂肪分解）。 通过脂肪酶的作用形成脂肪。迄今为止，还没有脂肪酶与蚊子的这一过程相关。此步骤之后是 TG 的重新合成并通过未表征的机制加载至 Lp。我们对埃及伊蚊的初步研究确定了一组脂肪酶、两种酰基转移酶和脂质转移蛋白 (LTP)，它们是储存在脂滴中的 TG 被动员的机制的组成部分。此外，蚊子幼虫脂肪体内的TG储存涉及脂滴储存蛋白1（Lsd1）。相比之下，Lsd2 在卵黄埃及伊蚊雌性的脂肪体中更为突出。作为我们持续研究的一部分，以了解昆虫中 TG 储存的动员​​过程，我们提出以下三个目标： 1- 确定参与埃及伊蚊脂肪体 TG 动员的主要脂肪体脂肪酶； 2-定义脂滴相关蛋白AaLsd1和AaLsd2在TG积累和动员中的作用； 3-研究酰基转移酶和LTP在埃及伊蚊TG合成和分泌机制中的作用。关于这种媒介蚊子脂质代谢的知识可以用来提高我们对几个生理方面的理解，例如卵子发生的调节、蚊子的适应性和生存。这些是制定控制病媒蚊种群的创新策略的相关方面。