A closer look at adipose tissue lymphatics and their markers

Abstract

Purpose of reviewLymphatic vessels are found in most tissues, with the exception of the cornea and the central nervous system. Tissues that have high exposure to antigens, such as the skin and the intestine, have especially extensive lymphatic vascular networks. Despite being densely vascularized with blood vessels, adipose tissue is poorly permeated with lymphatic vasculature. Here, we focus on the recent advances in the research on adipose tissue lymphatics and present a lymphatic-focused analysis of published single-cell and single-nucleus RNA sequencing datasets of adipose tissues.Recent findingsAlthough lymphatic expansion in obesity may limit inflammation and promote glycerol efflux from adipose tissue, lymphatic endothelial cells (LECs) secrete factors that reduce brown adipocyte thermogenesis. Transcriptomic analyses of these cells show that they express common lymphatic markers such as Proxl, but datasets from different studies show great variation in gene expression values due to the low number of captured LECs, depot differences, and species-specific gene expression patterns.SummaryAs the importance of LECs in the homeostasis of adipose tissue has become evident, investigators want to shed light on the specific interactions of lymphatics with other cell types in adipose tissues. Extracting LECs from readily available transcriptomics datasets provides a standpoint for investigators for future research. However, systematic studies are needed to reveal unique identities according to depot and species-specific LEC signatures.

Adipose tissue-derived microvascular fragments promote lymphangiogenesis in a murine lymphedema model

“…Beside abundant microvessels, the visceral adipose tissue of mice also contains a dense network of lymphatic vessels. 24 , 25 Consequently, MVF isolated from epididymal fat pads should be rich of lymphatic vessel fragments. 26 Indeed, we found that MVF contained individual LYVE-1 + lymphatic vessel fragments adjacent to the microvasculature.…”

“… 23 In line with this, the visceral adipose tissue of mice contains a recently described lymphatic vascular network. 24 , 25 Therefore, MVF may not only contain ADSC but also lymphatic vessel fragments and it can be assumed that they are particularly suitable building blocks for lymphatic tissue engineering. 16 , 26 In the present study, this hypothesis was tested by investigating the lymphangiogenic effects of MVF in a murine hindlimb lymphedema model.…”

Whole-mount immunofluorescence staining of blood and lymphatic vessels in murine small intestine

“…Podocalyxin is expressed on the luminal surface of the vasculature and is a useful marker for detecting blood and lymphatic vessels in various tissues. 2 , 3 , 4 LYVE1 is a more specific marker for mainly initial (capillary) lymphatic vessels. This protocol has also been used for other stainings using antibodies against vascular endothelial growth factor receptors 2 and 3 (KDR, FLT4), prospero homeobox protein 1 (PROX1), ETS-related gene (ERG), and vascular endothelial (VE)-cadherin (CDH5) in the adult murine small intestines.…”