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

Abstract

Purpose of review: In this review, we describe novel findings related to intestinal cholesterol 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 intestinal lipid transport can result in conditions such as dyslipidaemia and intestinal lymphangiectasia. Intestinal lymphatics also provide several 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.

Effects of liraglutide on the metabolism of triglyceride‐rich lipoproteins in type 2 diabetes

“…Liraglutide did not appear to alter the association between liver fat and VLDL 1 ‐triglyceride production, and therefore the decreased content of stored triglyceride in the liver may be sufficient to account for the decrease in VLDL 1 ‐triglyceride production on liraglutide. Another potential route for chylomicron fluxes is by transport into the lymphatic system 40,41 . Interestingly, lymphatic vessel dysfunction has been discovered in genetically modified mice 42 …”

Regulation of Lymphatic Function in Obesity

“…Vascular factors such as VEGF-C, angiopoietin-2, and DLL4 are reported to maintain VEcadherin junctional integrity and regeneration of lacteals (Zheng et al, 2014;Bernier-Latmani et al, 2015;Suh et al, 2019). These VE-cadherin intercellular button-like junctions allow fluid and chylomicrons into lacteals and, eventually, into blood circulation (Cifarelli and Eichmann, 2019;Hokkanen et al, 2019). Converting the lacteal LEC button junctions to zipper-like junctions prevents chylomicron entry into lacteals thus reducing lipid absorption and protection against dietinduced obesity.…”

“…The intestinal lymphatics are known as lacteals and are located centrally within each intestinal villus. Dietary fats are converted by enterocytes into triglyceriderich lipoproteins enveloped by proteins and cholesterol, which are called chylomicrons, and absorbed and transported by the intestinal lacteals by both passive and active contractile mechanisms (Choe et al, 2015;Escobedo and Oliver, 2017;Suh et al, 2018;Cifarelli and Eichmann, 2019;Hokkanen et al, 2019). Intestinal lacteals can also absorb fat-soluble vitamins.…”

Lymphatic Vessels Enhancing Adaptive Immunity Deteriorates Renal Inflammation and Renal Fibrosis

“…The first and foremost function of the lymphatics is to maintain tissue fluid homeostasis by removing the protein-rich lymph from the extracellular space to the blood circulation and absorption of fats in the gastrointestinal tract [16]. The initial lymphatics is the entrance of almost all dietary lipids, which are absorbed by intestinal cells and packaged into large lipoproteins (chylomicrons) and exported to the LVs [17]. In most tissues under physiological conditions, when plasma enters the capillary, there is continuous leakage of plasma into extracellular space [18].…”