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肠淋巴管及其在乳糜微粒吸收和脂质稳态中的作用。

Intestinal lymphatic vessels and their role in chylomicron absorption and lipid homeostasis.

机构信息

A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland.

Heart Center and Gene Therapy Unit, Kuopio University Hospital, Kuopio, Finland.

出版信息

Curr Opin Lipidol. 2019 Oct;30(5):370-376. doi: 10.1097/MOL.0000000000000626.

Abstract

PURPOSE OF REVIEW

In this review, we describe novel findings related to intestinal lipid transport in lymphatic vessels.

RECENT FINDINGS

Studies have shown that chylomicron entry to lacteals and lymph movement in intestinal lymphatic capillaries is an active process. Regulators of this intestinal chylomicron transport include among others the autonomous nervous system, transcription factors like PLAGL2, and molecular regulators, such as VEGF-A/Nrp1/VEGFR1, VEGF-C/VEGFR3, DLL4, CALCRL and GLP-2. Chylomicron transport in intestinal lymphatics is now emerging not only as an option for drug delivery but also as a new candidate for drug targeting in lipid-related disorders.

SUMMARY

Dysfunctions of lymphatic lipid transport can result in conditions such as dyslipidaemia. Intestinal lymphatics also provide several potential therapeutic possibilities: molecular regulation of lacteal cell-to-cell junctioning and lymph flow could provide new ways of treating conditions like hyperlipidaemia and associated diseases, such as atherosclerosis and other cardiovascular diseases, obesity, diabetes and fatty-liver disease. The intestinal lymphatic system can also be employed to deliver lipid nanoparticles as drug carriers to the venous circulation for improved treatment outcome. These findings highlight the importance and need for research on the different players of intestinal lymphatics in dietary lipid handling and therapeutic applications.

摘要

目的综述

在这篇综述中,我们描述了与肠道淋巴管内脂质转运相关的新发现。

最新发现

研究表明,乳糜微粒进入乳糜管和肠道淋巴管内的淋巴液运动是一个主动过程。调节肠道乳糜微粒转运的因素包括自主神经系统、PLAGL2 等转录因子以及 VEGF-A/Nrp1/VEGFR1、VEGF-C/VEGFR3、DLL4、CALCRL 和 GLP-2 等分子调节剂。肠道淋巴管中的乳糜微粒转运不仅为药物输送提供了新的选择,也为脂质相关疾病的药物靶向提供了新的候选途径。

总结

肠道淋巴管内脂质转运的功能障碍可能导致血脂异常等疾病。肠道淋巴管也提供了几种潜在的治疗可能性:乳糜管细胞间连接和淋巴流动的分子调节可能为治疗高脂血症和相关疾病(如动脉粥样硬化和其他心血管疾病、肥胖症、糖尿病和脂肪肝疾病)提供新方法。肠道淋巴管系统还可以用作将脂质纳米颗粒作为药物载体输送到静脉循环,以提高治疗效果。这些发现强调了研究肠道淋巴管在膳食脂质处理和治疗应用中不同参与者的重要性和必要性。

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