Mobilization of Triacylglycerol Stores in Insects

昆虫体内三酰甘油储存的动员

• 批准号: 7657019
• 负责人: Estela L. Arrese
• 金额: $ 26.25万
• 依托单位: OKLAHOMA STATE UNIVERSITY STILLWATER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-02-01 至 2012-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7657019
• 关键词: Adipocytes; Aedes; Affect; Amino Acid Sequence; Animals; Anopheles gambiae; Area; Arthropods; Biological Assay; Biology; Bombyx mori; Cells; Coupled; Cytosol; Drosophila melanogaster; Energy Metabolism; Enzymes; Equilibrium; Eukaryotic Cell; Evaluation; Family; Fat Body; Fatty Acids; Goals; Homologous Gene; Hydrolysis; Insect Control; Insecta; Investigation; Knowledge; Lipase; Lipid Biochemistry; Lipids; Lipolysis; Maintenance; Membrane Protein Traffic; Metabolic; Metabolic Pathway; Metabolism; Modeling; Molecular; Organelles; Organism; Oxidation-Reduction; Oxidoreductase; Pathway interactions; Phosphorylation; Phosphorylation Site; Physiological; Play; Process; Proline; Property; Protein Biosynthesis; Protein Family; Proteins; Proteomics; Reaction; Regulation; Reproduction; Role; Series; Signal Transduction; Sulfhydryl Compounds; Time; Tissues; Translating; Trehalose; Triglycerides; Vertebrates; Vitellogenesis; Whole Organism; base; dihydrolipoamide dehydrogenase; energy balance; genetic regulatory protein; human disease; improved; lipid metabolism; meetings; protein function; public health relevance; vector

DESCRIPTION (provided by applicant): Lipids, stored as triacylglycerol (TG), play an essential role as reserve of metabolic energy in insects. Utilization of fat body TG stores requires TG hydrolysis (lipolysis). Because fatty acids provide energy to other tissues as well as to the fat body cell, lipolysis must be coupled to multiple metabolic pathways. The long-term goal of this project is to understand the mechanism of regulation of lipolysis. During the previous period we identified two key components of the lipolytic pathway in insects. The main lipase found in the insect fat body, TG-lipase (TGL) homolog to Drosophila melanogaster CG8552, and a lipid droplet-associated protein, Lsd1, whose phosphorylation stimulates the rate of lipolysis. Lsd1 is one of the two PAT proteins, Lsd1 and Lsd2, of insect lipid droplets and plays a major role in the regulation of lipolysis. Lsd1 contains multiple conserved phosphorylation sites that regulate its activity. Lsd1 also has structurally conserved domains that are expected to play a role in its interaction with lipases and regulatory proteins and thus in the regulation of lipolysis. One of the goals of this project is to dissect the role of different regions of the Lsd1 molecule in the regulation of lipolysis. Other cytosolic and lipid droplet proteins, such as Lsd2, are expected to be involved in the regulation of lipolysis. This project also proposes to identify some of these proteins using a proteomic approach coupled to specific interaction assays and global studies to define differences in the protein composition of lipid droplets from several insects. Strong evidence indicating that the rate of lipolysis in the insect fat body is affected by the redox state of adipocytes led us to propose the investigation of this mechanism. Because the rate of TG hydrolysis must be modulated by signals originated from different pathways, we hypothesize that the redox state of the fat body cell, which is sensitive to multiple metabolic changes, plays a major role in the regulation of TG hydrolysis. In this project we will study the mechanism by which the redox state of the cell affects lipolysis. These studies will contribute to the understanding of the regulation of the utilization of energy stores in insects. This aspect of the biology of insects may be important to find mechanisms of control of insects that act as vectors of human diseases. PUBLIC HEALTH RELEVANCE: Energy metabolism and its regulation are key processes defining insect survival and reproduction. TGs are the predominant form of energy storage in all animals. The ability to store and release this energy involves a carefully regulated balance between TG synthesis and hydrolysis. Specialized mechanisms are expected in insects, including vectors of human diseases, to meet their unique metabolic needs, such as the capacity to mobilize massive amounts of lipid in a short period of time. These metabolic distinctions must be reflected in the molecular mechanisms involved in TG mobilization in insects. The long term goal of this project is to achieve a clear understanding of the regulation of triacylglycerol metabolism in insects.

描述（由申请人提供）：脂类以甘油三酯（TG）的形式储存，在昆虫体内起着代谢能量储备的重要作用。利用脂肪体储存的TG需要TG水解（脂解）。因为脂肪酸不仅为脂肪细胞提供能量，也为其他组织提供能量，所以脂肪分解必须与多种代谢途径相结合。该项目的长期目标是了解脂肪分解的调节机制。在之前的研究中，我们确定了昆虫脂肪分解途径的两个关键组成部分。在昆虫脂肪体中发现的主要脂肪酶，与果蝇CG8552同源的tg -脂肪酶（TGL），以及脂滴相关蛋白Lsd1，其磷酸化刺激脂肪分解的速度。Lsd1是昆虫脂滴的两种PAT蛋白Lsd1和Lsd2之一，在脂肪分解的调控中起主要作用。Lsd1含有多个调节其活性的保守磷酸化位点。Lsd1还具有结构保守的结构域，预计在其与脂肪酶和调节蛋白的相互作用中发挥作用，从而调节脂肪分解。该项目的目标之一是剖析Lsd1分子的不同区域在调节脂肪分解中的作用。其他细胞质和脂滴蛋白，如Lsd2，有望参与脂肪分解的调节。本项目还建议使用蛋白质组学方法，结合特异性相互作用分析和全局研究来鉴定其中一些蛋白质，以确定几种昆虫脂滴蛋白质组成的差异。强有力的证据表明，昆虫脂肪体的脂肪分解速率受到脂肪细胞氧化还原状态的影响，这使我们提出了对这一机制的研究。由于TG水解速率必须受到来自不同途径的信号调节，我们假设脂肪体细胞的氧化还原状态对多种代谢变化敏感，在TG水解的调节中起主要作用。在这个项目中，我们将研究细胞氧化还原状态影响脂肪分解的机制。这些研究将有助于了解昆虫能量储存利用的调控。昆虫生物学的这一方面对于找到控制作为人类疾病媒介的昆虫的机制可能很重要。公共卫生相关性：能量代谢及其调控是决定昆虫生存和繁殖的关键过程。tg是所有动物中主要的能量储存形式。储存和释放这种能量的能力涉及TG合成和水解之间精心调节的平衡。昆虫，包括人类疾病的媒介，预计会有专门的机制来满足其独特的代谢需求，例如在短时间内动员大量脂质的能力。这些代谢差异必须反映在昆虫TG动员的分子机制中。该项目的长期目标是明确了解昆虫体内三酰甘油代谢的调控。