Lipid and Lipoprotein Metabolism in Insects

描述(由申请人提供)：脂类，以三酰甘油(TAG)的形式储存，作为代谢能量的储备起着重要的作用。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。含有脂肪酸(FA)的脂肪在中肠的消化和加工，并运输到脂肪体储存是昆虫发育的关键。饮食中的胆固醇，也就是可以转化为胆固醇的甾醇，对昆虫来说是至关重要的，因为它们不能使甾醇脱脂。因此，甾醇的吸收和向组织的运输对昆虫的发育也是至关重要的。在过去的几年里，我们在阐明这些过程中涉及的代谢途径的大致轮廓方面取得了实质性进展。尚未解决的关键问题包括：1)FA和甾醇从肠腔吸收到中肠肠细胞的机制。2)血淋巴中脂蛋白脂蛋白与组织间的脂转移机制。3)中肠脂肪输出和脂肪体内脂肪储存的调节。我们建议通过追求以下特定目标来阐明涉及从中肠腔吸收脂肪并将其运输到脂肪体内储存部位的机制。 具体目的1.克隆和鉴定中肠脂肪酸和甾醇载体蛋白。我们将阐明FA和甾醇转运蛋白在脂肪从中肠腔吸收到中肠上皮中的作用。具体目的2.建立DAG转运的机制。我们将严格测试脂蛋白受体和LTP在DAG在组织和脂蛋白之间转移中的作用，并建立和定量检验DAG转运模型。具体目的3.建立胆固醇转运机制。我们将批判性地测试调节六分枝杆菌幼虫胆固醇稳态的群体作用假说。具体目标4.克隆和鉴定来自中肠和脂肪体的脂蛋白受体。我们将阐明脂蛋白受体在脂类转运中的作用。

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.