Lipid and Lipoprotein Metabolism in Insects

性状（由申请方提供）：脂质以三酰甘油（TAG）形式储存，作为代谢能量储备发挥重要作用。在全变态昆虫中，这些储备主要在幼虫阶段以TAG的形式积累在脂肪体中。脂肪酸在昆虫中肠的消化、加工和转运是昆虫发育的关键。饮食中的胆固醇，或可以转化为胆固醇的固醇，对昆虫来说是至关重要的，因为它们不能产生固醇。因此，甾醇的吸收及其向组织的运输对昆虫发育也至关重要。在过去的几年里，我们已经取得了实质性的进展，阐明了这些过程中所涉及的代谢途径的一般轮廓。关键的未解决问题包括：1）FA和固醇从管腔吸收到中肠肠细胞的机制。2)血淋巴脂蛋白脂质转运蛋白与组织间脂质转运的机制。3)中肠脂质输出和脂肪体脂质储存的调节。我们建议通过追求以下具体目标，以烟草天蛾幼虫为模型昆虫，阐明脂质从中肠腔吸收并运输到脂肪体储存部位的机制： 具体目标1.中肠脂肪酸和甾醇载体蛋白的克隆和鉴定。我们将阐明脂肪酸和固醇转运蛋白在脂质从中肠腔吸收到中肠上皮中的作用。建立DAG运输机制。我们将严格测试脂转运蛋白受体和LTP在DAG在组织和脂转运蛋白之间的转移中的作用，并且我们将开发和定量测试DAG运输的模型。建立胆固醇转运机制。我们将严格检验幼虫M中胆固醇稳态调节的质量作用假说。6.具体目标4。克隆和鉴定中肠和脂肪体中的载脂蛋白受体。我们将阐明载脂蛋白受体在脂质转运中的作用。

DESCRIPTION (provided by the applicant): Lipids, stored as triacylglycerol (TAG), play an essential role as a reserve of metabolic energy. In holometabolous insects, these reserves mainly accumulate during the larval stage in the form of TAG in the fat body. The digestion of fatty acid (FA) containing lipids and their processing in the midgut and transport to the fat body for storage are critical to insect development. Dietary cholesterol, or sterols that can be converted to cholesterol, are critical for insects because they cannot make sterols de riovo. Therefore, the absorption of sterols and their transport to tissues is also critical to insect development. Over the past several years we have made substantial progress in elucidating the general outline of the metabolic pathways involved in these processes. The critical unresolved issues include: 1) The mechanism by which FA and sterols are absorbed from the lumen into midgut enterocytes. 2) The mechanisms involved in lipid transfer between the hemolymph lipoprotein lipophorin and tissues. 3) The regulation of lipid export from midgut and lipid storage in the fat body. We propose to elucidate the mechanisms involved in lipid absorption from the midgut lumen and transport to sites of storage in the fat body using Manduca sexta larvae as a model insect through pursuit of the following specific aims: Specific aim 1. To clone and characterize fatty acid and sterol carrier proteins from the midgut. We will elucidate the role of FA and sterol transport proteins in lipid absorption from the midgut lumen into midgut epithelium.Specific aim 2. To establish the mechanism of DAG transport. We will critically test the role of lipophorin receptors and LTP in the transfer of DAG between tissues and lipophorin and we will develop and test quantitatively a model for DAG transport.Specific aim 3. To establish the mechanism of cholesterol transport. We will critically test the mass action hypothesis for the regulation of cholesterol homeostasis in larval M. sexta.Specific aim 4. To clone and characterize lipophorin receptors from the midgut and the fat body. We will elucidate the role of lipophorin receptors in lipid transport.