Visceral obesity and insulin resistance associate with CD36 deletion in lymphatic endothelial cells.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 34099721.
- Also identified by DOI 10.1038/s41467-021-23808-3 and PMC identifier 8184948.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Disruption of lymphatic lipid transport is linked to obesity and type 2 diabetes (T2D), but regulation of lymphatic vessel function and its link to disease remain unclear. Here we show that intestinal lymphatic endothelial cells (LECs) have an increasing CD36 expression from lymphatic capillaries (lacteals) to collecting vessels, and that LEC CD36 regulates lymphatic integrity and optimizes lipid transport. Inducible deletion of CD36 in LECs in adult mice (Cd36<sup>ΔLEC</sup>) increases discontinuity of LEC VE-cadherin junctions in lacteals and collecting vessels. Cd36<sup>ΔLEC</sup> mice display slower transport of absorbed lipid, more permeable mesenteric lymphatics, accumulation of inflamed visceral fat and impaired glucose disposal. CD36 silencing in cultured LECs suppresses cell respiration, reduces VEGF-C-mediated VEGFR2/AKT phosphorylation and destabilizes VE-cadherin junctions. Thus, LEC CD36 optimizes lymphatic junctions and integrity of lymphatic lipid transport, and its loss in mice causes lymph leakage, visceral adiposity and glucose intolerance, phenotypes that increase risk of T2D.
Medical subject headings
- CD36 Antigens
- Endothelial Cells
- Insulin Resistance
- Obesity, Abdominal