Lacteal junction zippering protects against diet-induced obesity

被引：171

作者：

Zhang, Feng ^{[1
]}

Zarkada, Georgia ^{[1
]}

Han, Jinah ^{[1
]}

Li, Jinyu ^{[1
]}

Dubrac, Alexandre ^{[1
]}

Ola, Roxana ^{[1
,2
]}

Genet, Gael ^{[1
]}

Boye, Kevin ^{[1
]}

Michon, Pauline ^{[1
,3
]}

Kunzel, Steffen E. ^{[1
]}

Camporez, Joao Paulo ^{[4
]}

Singh, Abhishek K. ^{[5
,6
,7
]}

Fong, Guo-Hua ^{[8
]}

Simons, Michael ^{[1
]}

Tso, Patrick ^{[9
]}

Fernandez-Hernando, Carlos ^{[5
,6
,7
]}

Shulman, Gerald I. ^{[4
,10
]}

Sessa, William C. ^{[11
]}

Eichmann, Anne ^{[1
,3
,10
]}

机构：

[1] Yale Univ, Sch Med, Cardiovasc Res Ctr, 333 Cedar St, New Haven, CT 06510 USA

[2] Univ Transylvania, Dept Basic Prevent & Clin Sci, Brasov 500019, Romania

[3] Paris Cardiovasc Res Ctr, INSERM, U970, F-75015 Paris, France

[4] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA

[5] Yale Univ, Sch Med, Vasc Biol & Therapeut Program, Dept Community Med, New Haven, CT USA

[6] Yale Univ, Sch Med, Vasc Biol & Therapeut Program, Dept Pathol, New Haven, CT USA

[7] Yale Univ, Sch Med, Integrat Cell Signaling & Neurobiol Metab Program, New Haven, CT USA

[8] Univ Connecticut, Hlth Ctr, Dept Cell Biol, Farmington, CT 06030 USA

[9] Univ Cincinnati, Metab Dis Inst, Dept Pathol & Lab Med, Cincinnati, OH 45237 USA

[10] Yale Univ, Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06510 USA

[11] Yale Univ, Sch Med, Dept Pharmacol, Vasc Biol & Therapeut Program, New Haven, CT 06510 USA

来源：

SCIENCE | 2018年 / 361卷 / 6402期

关键词：

ENDOTHELIAL-CELLS; VEGF-C; LIPOPROTEINS; MECHANISMS; TRANSPORT; GROWTH; CHYLOMICRONS; ANGIOGENESIS; INFLAMMATION; INTEGRITY;

D O I：

10.1126/science.aap9331

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 (Nrpl) 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.

引用

页码：599 / 603

页数：5

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