Mobilization of Triacylglycerol Stores in Insects

 描述(申请人提供)：蚊子是一些人类疾病的媒介，对全世界的公共卫生构成严重问题。世界上一半的人口面临疟疾，而登革热是100多个国家的永久威胁，每年有5000-1亿人感染。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，这种方法受到了赋予蚊子抗药性的新机制的威胁。缺乏预防或治愈蚊子传播疾病的疫苗或药物，突显了制定控制蚊子数量的替代战略的必要性。对蚊子生物学的详细了解是制定新的媒介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脂肪储存和动员的机制。能量储备对于繁殖的重要性在蚊子身上是显而易见的，比如成年雌性埃及伊蚊。这些雌性企鹅储存的营养水平较低，它们需要一顿血餐来获得额外的营养，以完成生殖周期。在一顿血餐之后，蛋白质和脂肪储备在脂肪体中合成，并通过血淋巴运输到卵巢。脂质储备是通过脂蛋白(LP)运输的。埃及伊蚊的一个显著特征是Lp携带甘油三酯。此功能 将蚊子与大多数LP携带二酰甘油(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肪动员的关键方面。甘油三酯向卵巢的转移是一个复杂的过程，从储存在卵巢中的甘油三酯(脂肪分解)的水解开始。 由于脂肪酶的作用而使身体发胖。到目前为止，还没有脂肪酶与蚊子的这一过程有关。这一步之后是TG的重新合成，并通过未知的机制负载到LP上。我们在埃及按蚊的初步研究确定，一组脂肪酶、两个酰基转移酶和脂类转移蛋白(LTP)是储存在脂滴中的甘油三酯被动员的机制的组成部分。此外，蚊子幼虫脂肪体中的TG储存涉及脂滴储存蛋白1(LSD1)。相比之下，Lsd2在产黄性埃及伊蚊雌性的脂肪体中更为显著。作为了解昆虫TG储存动员过程的持续研究的一部分，我们提出了以下三个目标：1-鉴定参与埃及斑潜蝇脂肪体TG动员的主要脂肪体脂肪酶；2-确定脂滴相关蛋白AaLsd1和AaLsd2在TG积累和动员中的作用；3-研究酰基转移酶和LTP在埃及斑潜蝇TG合成和分泌机制中的作用。对这种媒介蚊体内脂类代谢的了解可以提高我们对几个生理方面的理解，如卵子发生的调节、蚊子的健康状况和生存。这些都是制定控制媒介蚊子种群的创新战略的相关方面。

 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.