Lipidome Remodeling During Development of T1D

T1D 发展过程中的脂质组重塑

• 批准号: 10094214
• 负责人: Qibin Zhang
• 金额: $ 35.49万
• 依托单位: UNIVERSITY OF NORTH CAROLINA GREENSBORO
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-02-01 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10094214
• 关键词: Animal Model; Antigens; Autoimmune Diseases; Beta Cell; Biological Process; Cell Death; Cells; Cellular Membrane; Clinical; Communities; Complement; Complex; Development; Disease; Dissociation; Etiology; Glycolipids; Glycosphingolipids; Goals; Human; Inbred NOD Mice; Insulin-Dependent Diabetes Mellitus; Isotope Labeling; Label; Lipids; Liquid Chromatography; Measures; Mediating; Mediator of activation protein; Methods; Molecular; Organism; Ozone; Pathogenesis; Pathologic; Pattern; Peptides; Physiology; Positioning Attribute; Proteins; Protocols documentation; Recovery; Reproducibility; Research; Resolution; Resources; Role; Signal Transduction; Structure; Structure of beta Cell of islet; Symptoms; T-Lymphocyte; Techniques; Technology; Tissues; Transcript; Unsaturated Fats; Variant; Vertebral column; base; biological systems; human disease; human model; improved; interest; lipid mediator; lipid metabolism; lipidome; lipidomics; mouse model; pi bond; public health relevance; stable isotope; tool; two-dimensional

Project Summary/Abstract DESCRIPTION: Lipids are essential cellular components and act as mediators in cell signaling. The function of lipids is determined by their structures. Dysregulated lipid metabolism is associated with a variety of pathological conditions, including Type 1 Diabetes (T1D). The levels of lipids cannot be predicted by the transcripts or proteins. To understand more about the role of lipids in the development of T1D, an important first step is to directly measure the temporal changes of lipids in an organism that shares similar physiology with human T1D. Built on our technological advancements in comprehensive global lipidomics, targeted lipidomic analysis of lipid mediators, isobaric labeling-based multiplexed analysis of intact glycolipids and determination of C=C unsaturation in intact lipids, in this project, we aim to profile the longitudinal changes of the nonobese diabetic (NOD) mouse lipidome during different stages of T1D development by accomplishing the following: 1) in-depth profile and accurately quantify the major lipids in T1D-pertinent tissues using global lipidomics; 2) use advanced technologies to improve structural resolution, accurately identify and quantify glycolipids and broadly profile bioactive lipid mediators; and 3) compare lipid expression profiles in different tissues and characterize lipidome remodeling during different stages of T1D development. Successfully accomplishing these goals will not only provide invaluable resource to the research community interested in the role of lipids in the development of T1D, but it will also provide better practices for conducting lipidomics research in general.

项目摘要/摘要 描述：脂类是细胞的基本成分，在细胞信号转导中起中介作用。的功能 脂类由其结构决定。脂代谢紊乱与多种疾病有关 病理情况，包括1型糖尿病(T1D)。血脂水平不能通过 转录本或蛋白质。为了更多地了解血脂在T1D发病中的作用，T1D是一种重要的 第一步是直接测量具有相似生理特征的生物体中脂质的时间变化。 与人类的T1D。以我们在全面全球脂质组学方面的技术进步为基础，有针对性 脂类介体的脂组学分析，基于等压标记的完整糖脂和 完整脂质中C=C不饱和度的测定，在这个项目中，我们的目标是描绘出 非肥胖糖尿病(NOD)小鼠在T1D发育的不同阶段通过完成 1)深入剖析和准确定量T1D相关组织中的主要脂类 脂质组学；2)利用先进技术提高结构分辨率，准确鉴定和量化 糖脂和广谱生物活性脂质介体；以及3)比较不同组织中的脂质表达谱。 T1D发育不同阶段的组织和脂体重塑的特征。成功 实现这些目标不仅将为感兴趣的研究界提供宝贵的资源 脂类在T1D发生中的作用，但它也将为进行脂质组学提供更好的实践 总体而言，研究。