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）：蚊子是多种人类疾病的传播媒介，对全球公共卫生构成严重问题，而登革热对 100 多个国家的 50-1 亿人口构成永久威胁。为了控制蚊子传播的疾病，传统上是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。缺乏预防或治疗传播性蚊子疾病的疫苗或药物强调需要制定控制蚊子种群的替代策略。在这种情况下，我们建议详细了解蚊子生物学是制定新的媒介控制策略的先决条件。研究媒介蚊子埃及伊蚊的脂肪储存和动员机制 能量储备对于繁殖的重要性在蚊子中是显而易见的，例如成年雌性埃及伊蚊。一个血粉获得额外的营养以完成生殖周期。 血粉后，蛋白质和脂质储备在脂肪体内合成，并通过血淋巴运输到卵巢。脂质储备是由脂蛋白 (Lp) 运输的。埃及伊蚊是Lp携带TG。 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中脂质动员的关键方面。TG 转移到卵巢是一个复杂的过程，从 TG 的水解开始。脂肪分解）储存在 到目前为止，还没有脂肪酶与蚊子中的这一过程相关，然后通过我们对埃及伊蚊的初步研究确定了一组 TG 的重新合成和 Lp 的加载。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被动员的机制的组成部分。此外，TG储存在脂肪体内。蚊子幼虫涉及脂滴储存蛋白 1 (Lsd1)，相比之下，Lsd2 在卵黄埃及蚊的脂肪体中更为突出，作为我们继续研究昆虫 TG 储存动员过程的一部分，我们建议。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- 确定脂质的作用；液滴相关蛋白 AaLsd1 和 AaLsd2 在 TG 的积累和动员中的作用；3- 研究酰基转移酶和 LTP 在埃及伊蚊的 TG 合成和分泌机制中的作用。蚊子媒介可用于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，这些都是与控制媒介的创新策略的发展相关的方面。蚊子种群。