Novel approached to prevent diet-induced obesity via lacteal junctions

通过乳腺连接预防饮食引起的肥胖的新方法

基本信息

批准号：
10394841
负责人：
Anne Christine Eichmann
金额：
$ 37.69万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-07-01 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10394841
关键词：
Address Atherosclerosis Biological Biology Blood Circulation Cardiovascular Diseases Cells Chronic Chylomicrons Clinical Data Diet Dietary Fats Disease Drainage procedure Endothelium Event Fluid Balance Functional disorder Genetic Genetic Models Glaucoma Goals Growth Factor Receptors Health Immune Inflammation Inflammatory Intestines KDR gene Knowledge Lead Lipids Lymph Lymphatic Lymphatic Capillaries Lymphatic Diseases Lymphatic function Lymphedema Mediating Metabolic Diseases Molecular Mus Myocarditis Nerve Degeneration Neurodegenerative Disorders Obesity Pathway interactions Pharmacology Public Health RHOA gene ROCK1 gene Regulation Resistance Resolution Role Signal Transduction Small Intestines System Testing Therapeutic Uses Tissues Vascular Endothelial Growth Factors Veins absorption base diet-induced obesity experimental study improved in vivo lacteal loss of function lymphatic drainage lymphatic dysfunction lymphatic vessel macromolecule mouse model novel novel strategies obesity management postnatal prevent receptor function therapeutic target trafficking uptake

项目摘要

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.

项目摘要淋巴管控制所有身体组织中的流体稳态和免疫细胞循环，脂质小肠中的吸收。它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在终端之间分配劳动力通过开放式按钮连接吸收淋巴的淋巴毛细血管，以及将淋巴运送到淋巴的收集器静脉，具有更紧密的拉链连接。我们在这里解决了LEC按钮和拉链连接的角色健康和疾病，假设LEC连接操作为临床提供了新的机会设置。我们已经表明，肠道乳酸的拉链可防止乳糜微粒的吸收和渲染抗饮食诱导的肥胖症的小鼠促使我们研究了诱导形成的分子机制按钮和拉链，并测试它们对脂质摄取，肥胖和炎症的影响。集体，拟议的研究将阐明内皮生物学的尚未研究的方面并确定分子基于这种知识的机制和新方法，可以通过这种知识来减少肥胖拉链形成，可以通过按钮与淋巴功能障碍相关的疾病有效。