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Publication
Lacteal junction zippering protects against diet-induced obesity.
Authors Zhang F, Zarkada G, Han J, Li J, Dubrac A, Ola R, Genet G, Boyé K, Michon P,
Künzel SE, Camporez JP, Singh AK, Fong GH, Simons M, Tso P, Fernández-Hernando
C, Shulman GI, Sessa WC, Eichmann A
Submitted By Submitted Externally on 2/22/2019
Status Published
Journal Science (New York, N.Y.)
Year 2018
Date Published 8/1/2018
Volume : Pages 361 : 599 - 603
PubMed Reference 30093598
Abstract Excess dietary lipid uptake causes obesity, a major global health problem.
Enterocyte-absorbed lipids are packaged into chylomicrons, which enter the
bloodstream through intestinal lymphatic vessels called lacteals. Here, we show
that preventing lacteal chylomicron uptake by inducible endothelial genetic
deletion of Neuropilin1 (Nrp1) and Vascular endothelial growth factor receptor 1
(Vegfr1; also known as Flt1) renders mice resistant to diet-induced obesity.
Absence of NRP1 and FLT1 receptors increased VEGF-A bioavailability and
signaling through VEGFR2, inducing lacteal junction zippering and chylomicron
malabsorption. Restoring permeable lacteal junctions by VEGFR2 and vascular
endothelial (VE)-cadherin signaling inhibition rescued chylomicron transport in
the mutant mice. Zippering of lacteal junctions by disassembly of cytoskeletal
VE-cadherin anchors prevented chylomicron uptake in wild-type mice. These data
suggest that lacteal junctions may be targets for preventing dietary fat uptake.




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