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（由适用提供）：蚊子是许多人类疾病的向量，代表了全球公共卫生的严重问题。全球一半的人口暴露于疟疾，而粉丝在每年感染了5,0-1亿个人的100多个国家中是永久威胁。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。但是，这种方法受到新机制会议蚊子抗药性的威胁。缺乏预防或治愈蚊子传播疾病的疫苗或药物，这是制定控制蚊子种群的替代策略的必要性。对蚊子生物学的详细理解是发展新向量控制策略的先决条件。在这种情况下，我们建议研究载体蚊子埃德斯埃及埃及的脂肪存储的存储和动员的机制。能量储量在繁殖中的重要性在蚊子中很明显，例如成年雌性A. aegypti。这些雌性储存低水平的养分，他们需要血液粉才能获得更多的营养，以完成复制周期。血液粉后，蛋白质和脂质储量在脂肪体中合成，并通过血淋巴运输到卵巢。脂质储备由皮寄生蛋白（LP）运输。 A. aegypti的一个显着特征是LP携带TG。此功能 将蚊子与大多数昆虫分离，其中LP携带二酰基甘油（DG）。在这个项目中，我们建议研究A. eegypti中脂质动员的关键方面。 TG向卵巢的转移是一个复杂的过程，从存储在TG（脂解）的水解开始 脂肪酶的作用。到目前为止，在蚊子中尚无脂肪酶与此过程有关。此步骤之后是TG的重新合成，并通过未表征的机制将其加载到LP。我们在A. egypti中的初步研究确定了一组脂肪酶，两个酰基转移酶和脂质转移蛋白（LTP）是动员脂质液滴中TG的组成部分。此外，脂肪体幼虫蚊子中的TG储存涉及脂质液滴储存蛋白1（LSD1）。相比之下，LSD2在植物生成的脂肪体中更为突出。作为了解昆虫中TG存储的过程的继续研究的一部分，我们提出了以下三个目标：1-确定与A. Aegypti中脂肪体TG动员TG有关的主要脂肪体脂肪酶； 2要定义脂质液滴相关蛋白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在合成机理中的作用和Tg在A. eegypti中的分泌。可以应用有关该载体蚊子中脂质代谢的知识，以提高我们对几个物理方面的理解，例如调节卵子，蚊子适应性和生存。这些是控制媒介蚊子人口的创新策略的相关方面。