Quantifying the role of lymphatics in lipid metabolism and transport

项目摘要-淋巴循环的研究是令人兴奋的，也是充满挑战的，因为它很重要 在免疫细胞交易中，癌症转移和脂类代谢越来越受到重视。 而且由于它在这些过程中的积极作用直到现在才被发现。因为这件事很复杂 因此，迫切需要开发新的量化工具和模型，并使用这些工具和模型 以跨学科的方式探索这些积极作用的新工具。这项建议涉及到积极的作用 淋巴管在脂质运输和新陈代谢中的作用，这是一个知之甚少的话题，对于这个话题， 几乎没有研究它的工具。我们将通过三个具体目标解决这些问题：1)确定和量化 脂类跨淋巴管内皮细胞转运的关键受体和蛋白的作用 使用我们以前开发的乳汁组织工程模型；2)开发和表征一种 肠系膜淋巴管摄取脂质的活体模型，并使用该模型评估 全球淋巴功能受损(在基因敲除小鼠中)对淋巴管摄取脂质的影响；3) 确定高脂血症对淋巴功能的影响(特别是内源性功能 淋巴泵)使用体外、体内和分离血管模型的组合。这三个人加在一起 AIMS将研究脂质和淋巴功能的平衡，并提供对由此产生的 淋巴或脂质功能障碍对脂质平衡和组织液平衡的影响。

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.