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Review
. 2022 Jan 1;163(1):bqab224.
doi: 10.1210/endocr/bqab224.

Crosstalk Between Adipose and Lymphatics in Health and Disease

Gregory P Westcott  1   2   3 , Evan D Rosen  1   3   4
Affiliations
Review

Crosstalk Between Adipose and Lymphatics in Health and Disease

Gregory P Westcott et al. Endocrinology. .

Abstract

Adipose tissue, once thought to be an inert receptacle for energy storage, is now recognized as a complex tissue with multiple resident cell populations that actively collaborate in response to diverse local and systemic metabolic, thermal, and inflammatory signals. A key participant in adipose tissue homeostasis that has only recently captured broad scientific attention is the lymphatic vasculature. The lymphatic system's role in lipid trafficking and mediating inflammation makes it a natural partner in regulating adipose tissue, and evidence supporting a bidirectional relationship between lymphatics and adipose tissue has accumulated in recent years. Obesity is now understood to impair lymphatic function, whereas altered lymphatic function results in aberrant adipose tissue deposition, though the molecular mechanisms governing these phenomena have yet to be fully elucidated. We will review our current understanding of the relationship between adipose tissue and the lymphatic system here, focusing on known mechanisms of lymphatic-adipose crosstalk.

Keywords: adipose tissue; lipedema; lymphatic endothelium; lymphedema; obesity.

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Figures

Figure 1.
Figure 1.
Lymphatic system organization and anatomy. (A) Schematic of major lymphatic anatomic and functional characteristics. (B) Confocal image of a perigonadal fat pad whole mount dissected from a mouse in which lymphatic vasculature was labeled by Prox1-CreER-driven tdTomato expression (purple). Scale bar: 300 μm. (C) A lymphatic vessel and valve labeled by NTS-Cre-driven tdTomato (red) in a murine mesenteric fat whole mount. Scale bar: 50 μm. LEC, lymphatic endothelial cell.
Figure 2.
Figure 2.
The bidirectional and cyclical relationship between lymphatics and adipose tissue. Obesity leads to defects in lymphatic structure and function and an increased risk of lymphedema, while lymphedema leads to abnormal adipose expansion. LV, lymphatic vessel.
Figure 3.
Figure 3.
The lymphatic endothelial cell-adipocyte axis. Specific mechanisms of adipocyte-lymphatic endothelial cell (LEC) crosstalk have recently been described. Neurotensin (NTS) is secreted by LECs and can act via NTS receptor 2 (NTSR2) on brown adipocytes to suppress extracellular signal-regulated kinase (ERK) signaling and reduce thermogenesis. In addition to its direct action on adipocytes via β-adrenergic receptors (ADRBs), norepinephrine also stimulates thermogenesis by agonism of the α2-adrenergic receptor (ADRA2) on LECs, which in turn suppresses NTS production, thereby releasing thermogenic components from NTS inhibition. Specific adipocyte-derived factors that affect LEC function include leptin and adiponectin, which have been demonstrated to inhibit and promote lymphangiogenesis, respectively. Additional mediators of the LEC-adipocyte axis are likely to be important in further defining the relationship between adipose tissue and lymphatic dysfunction.
See this image and copyright information in PMC

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