Mobilization of Triacylglycerol Stores in Insects

Oklahoma State University Stillwater, Stillwater OK

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Abstract

? 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.