Lipid and Lipoprotein Metabolism in Insects

昆虫的脂质和脂蛋白代谢

• 批准号: 6541401
• 负责人: MICHAEL A WELLS
• 金额: $ 35.1万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-07-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6541401
• 关键词: Manduca; cell line; cholesterol; diacylglycerols; electron microscopy; fat body; fatty acid transport; gastrointestinal absorption /transport; hemolymph; immunoprecipitation; larva; lipid biosynthesis; lipid metabolism; lipid transport; northern blottings; nutrition related tag; protein structure function; receptor binding; sterols; transport proteins; triglycerides; western blottings

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.

描述（由申请人提供）：脂质存储为三酰基甘油（TAG），作为代谢能力储备的重要作用。在单代昆虫中，这些储量主要在幼虫阶段以脂肪体标签的形式积累。含脂质的脂肪酸（FA）的消化及其在中肠和运输到脂肪体以存储的脂肪酸（FA）对于昆虫发育至关重要。饮食中胆固醇或可以转化为胆固醇的固醇对昆虫至关重要，因为它们不能生产硫醇。因此，固醇的吸收及其传输到组织也对昆虫发育至关重要。在过去的几年中，我们在阐明这些过程中涉及的代谢途径的一般轮廓方面取得了重大进展。关键的未解决的问题包括：1）FA和固醇从管腔吸收到中肠肠细胞中的机制。 2）与脂质蛋白脂蛋白和组织之间脂质转移有关的机制。 3）调节脂肪体中肠和脂质储存的脂质导出。我们建议阐明使用Manduca sexta幼虫从中肠腔中涉及脂质吸收的机制，并运输到脂肪体中的储存位置，以追求以下特定目的： 特定目的1。要克隆并表征来自中肠的脂肪酸和固醇载体蛋白。我们将阐明FA和固醇转运蛋白在中肠腔中的脂质吸收中的作用。特定的目标2。建立DAG转运的机理。我们将批判性地测试亲脂蛋白受体和LTP在组织和脂素之间DAG转移中的作用，我们将在定量上开发和测试DAG转运的模型。特异性目标3。建立胆固醇转运的机制。我们将批判性地检验质量作用假设，以调节幼虫M. sexta中的胆固醇稳态。特异性目标4。以克隆和表征来自中肠和脂肪体的脂透蛋白受体。我们将阐明亲脂蛋白受体在脂质转运中的作用。