Novel approached to prevent diet-induced obesity via lacteal junctions

项目摘要 淋巴管控制着体内所有组织中的液体动态平衡和免疫细胞循环，以及脂质 在小肠中吸收。他们的功能障碍与心血管、代谢和 神经退行性疾病。正常的淋巴功能需要终端之间的分工 通过开放的按钮连接吸收淋巴的毛细淋巴管，以及将淋巴输送到 静脉，它有更紧密的拉链连接。我们在这里介绍LEC纽扣和拉链连接在 健康和疾病，假设LEC连接操作在临床上提供了新的机会 设置。我们已经证明，拉链可以阻止乳糜粒的吸收和分泌。 小鼠对饮食诱导的肥胖具有抵抗力，促使我们研究诱导肥胖的分子机制 并测试它们对脂肪摄取、肥胖和炎症的影响。总体而言， 拟议的研究将阐明内皮生物学尚未被研究的一个方面，并确定分子 基于这一知识的机制和新方法可能有助于通过 拉链形成和可能是有效的疾病与淋巴功能障碍通过纽扣。

Project Summary Lymphatic vessels control fluid homeostasis and immune cell circulation in all body tissues, and lipid absorption in the small intestine. Their dysfunction is implicated in cardiovascular, metabolic and neurodegenerative disease. Normal lymphatic function requires a division of labor between terminal lymphatic capillaries that uptake lymph via open button junctions, and collectors that transport lymph to the veins, which have tighter zipper junctions. We here address the role of LEC button and zipper junctions in health and disease, with the hypothesis that LEC junction manipulation offers novel opportunities in clinical settings. We have shown that zippering of intestinal lacteals prevents chylomicron absorption and renders mice resistant to diet-induced obesity, prompting us to investigate molecular mechanisms inducing formation of buttons and zippers and test their implication in lipid uptake, obesity and inflammation. Collectively, the proposed studies will elucidate an as yet understudied aspect of endothelial biology and identify molecular mechanisms and novel approaches based on this knowledge that could be useful to reduce obesity via zipper formation and may be effective in diseases associated with lymphatic dysfunction via buttons.