Quantifying the role of lymphatics in lipid metabolism and transport

量化淋巴管在脂质代谢和运输中的作用

• 批准号: 7929080
• 负责人: James Brandon Dixon
• 金额: $ 23.36万
• 依托单位: GEORGIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-10 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7929080
• 关键词: Address; Affect; Animal Model; Biology; Blood; CD36 gene; Caveolins; Cells; Chylomicrons; Clinical; Disease; Endothelial Cells; Equilibrium; Fluid Balance; Functional disorder; Gene Expression Microarray Analysis; Gene Silencing; Homeostasis; Immune; In Vitro; Intestines; Knockout Mice; Link; Lipids; Lipoproteins; Low Density Lipoprotein Receptor; Lymphatic; Lymphatic Endothelial Cells; Lymphatic Endothelium; Lymphatic System; Lymphedema; Membrane; Mesentery; Metabolism; Methods; Modeling; Neoplasm Metastasis; Obesity; Pharmaceutical Preparations; Phase; Process; RNA; Research; Research Project Grants; Research Project Summaries; Role; System; Techniques; Time; Tissue Engineering; Tissues; Work; absorption; design; in vitro Model; in vivo; in vivo Model; insight; lipid metabolism; lipid transport; lymphatic circulation; lymphatic pump; receptor; tool; transcytosis; uptake

Project Summary - Research in the lymphatic circulation is exciting and rich in challenges as its importance in immune cell trafficl<ing, cancer metastasis, and lipid metabolism are quicl<ly becoming more appreciated and as its active roles in such processes are only now being discovered. Because of the complexity of this system, there is great need for new and quantitative tools and models to be developed, and to use those new tools to explore these active roles in interdisciplinary manners. This proposal addresses the active role of lymphatics in lipid transport and metabolism, a topic which is very poorly understood and for which very few tools exist to study It. We will address these issues through three specific aims: 1) Identify and quantify the role of key receptors and proteins involved in the transcytosis of lipid across lymphatic endothelial cells using our previously developed tissue engineered model of the lacteal; 2) develop and characterize an in vivo model of lymphatic uptake of lipid by mesenteric lymphatics and use this model to assess the consequences of globally impaired lymphatic function (in knock-out mice) on lipid uptake by lymphatics; 3) determine the effects of hyperiipidemia on lymphatic function (particularly the function of the intrinsic lymphatic pump) using a combination of in vitro, in vivo, and isolated vessel models. Collectively these three aims will investigate the balance of lipid and lymphatic function and provide new insight into the resulting consequences of lymphatic or lipid dysfunction on lipid homeostasis and tissue fluid balance.

项目摘要 - 淋巴流通的研究令人兴奋，挑战是其重要性 在免疫细胞流量中，癌症转移和脂质代谢变得更加赞赏 而且，由于它在此类过程中的积极角色直到现在才被发现。由于这个复杂性 系统，非常需要开发新的和定量的工具和模型，并使用这些工具和模型 在跨学科举止中探索这些积极角色的新工具。该提议解决了积极的角色 脂质运输和代谢中的淋巴管，这个话题非常了解，并且非常 很少有工具可以研究它。我们将通过三个特定目的解决这些问题：1）识别和量化 关键受体和蛋白质参与淋巴内皮细胞脂质转胞膜的作用 使用我们先前开发的乳酸组织工程模型； 2）开发和表征 肠系膜淋巴机对脂质的淋巴摄取的体内模型，并使用此模型评估 全球受损的淋巴功能（在敲除小鼠中）对淋巴管摄取脂质的后果； 3） 确定高脂肪血症对淋巴功能的影响（尤其是内在的功能 淋巴泵）使用体外，体内和孤立的血管模型的组合。这三个集体 目标将研究脂质和淋巴功能的平衡，并为此提供新的见解 淋巴或脂质功能障碍对脂质稳态和组织液平衡的后果。