Lacteal junction zippering protects against diet-induced obesity
Open accessAbstract
Zipping up obesity: Chylomicrons are specialized particles that carry dietary fats from the intestine to the bloodstream for absorption into the body. Lacteals are lymphatic vessels that act as the highway for chylomicron transport, but it is unclear how passage occurs. Zhang et al. report that two endothelial cell receptors, neuropilin-1 (NRP1) and vascular endothelial growth factor receptor 1 (VEGFR1, also known as FLT1), are required to convert the entry spaces between lacteals from open junctions to closed, zipped structures (see the Perspective by McDonald). Mice that were fed a high-fat diet were subsequently rendered resistant to weight gain if NRP1 and FLT1 were inactivated. Science , this issue p. 599 ; see also p. 551
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Button junctions can convert into zipper junctions in some disease states and revert back to buttons under appropriate experimental conditions.
“Button junctions can convert into zipper junctions in some disease states and revert back to buttons under the appropriate experimental conditions (25).”
From Transport and Immune Functions of the Lymphatic System. (2025) · cites this paper as [25]
The paper reports button-to-zipper changes in mouse lacteals after genetic deletion of Nrp1 and Flt1, and fewer zipper-like junctions after dexamethasone treatment of some mutant mice (Abstract; page not provided). This supports experimentally induced, reversible junction changes, but it does not establish that the button-to-zipper conversion occurs in disease states. (LLM, conf=0.86)
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- Authors
- Zhang, F., Zarkada, G., Han, J., Li, J., Dubrac, A., Ola, R., Genet, G., Boyé, K., Michon, P., Künzel, S. E., Camporez, J. P., Singh, A. K., Fong, G.-H., Simons, M., Tso, P., Fernández-Hernando, C., Shulman, G. I., Sessa, W. C., & Eichmann, A.
- Affiliations
- Yale University (US)
- Transilvania University of Brașov (RO)
- Cardiovascular Research Center, Yale University School of Medicine, New Haven, CT 06510-3221, USA.
- Inserm (FR)
- Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA.
- UConn Health (US)
- University of Cincinnati (US)
- Departments of Comparative Medicine and Pathology, Vascular Biology and Therapeutics Program and Integrative Cell Signaling and Neurobiology of Metabolism Program, Yale University School of Medicine, New Haven, CT, USA.
- Corresponding author
- Eichmann, Anne
- ORCID
- Venue
- Science
- Published
- 2018-08-10
- Volume
- 361
- Issue
- 6402
- Pages
- 599-603
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC6317738
- OpenAlex
- W2885974208
- Cited by
- 237
- References
- 52
- Citations by year
- 2026: 21 · 2025: 29 · 2024: 25 · 2023: 43 · 2022: 39 · 2021: 35 · 2020: 25 · 2019: 13 · 2018: 7
- FWCI
- 7.52
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (1R01HLI125811, 2T32HL7950-16A1)
- National Eye Institute (1R01EY025979-01)
- American Heart Association (14POST20380207, 15POST25560114)
- Agence Nationale de la Recherche (ANR Ghandi, Brainwash)
- EMBO Long-Term Fellowships (ALTF 87-2016)
- Topics
- Health Sciences › Medicine › Oncology › Lymphatic System and Diseases
- Health Sciences › Medicine › Surgery › Lymphatic Disorders and Treatments
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Keywords
- lacteals, diet-induced obesity, neuropilin-1, Flt-1, VEGFR1, endothelial cell receptors, lymphatic vessels, high-fat diet, intestinal lipid absorption
- MeSH terms
- Cadherin 5, Animals, Chylomicrons, Dietary Fats, Intestinal Absorption, Male, Obesity, Signal Transduction, Antigens, CD, Cadherins, Gene Deletion, Mice, Knockout, Enterocytes, Neuropilin-1, Vascular Endothelial Growth Factor Receptor-1, Vascular Endothelial Growth Factor Receptor-2, Vascular Endothelial Growth Factor A, Mice, Diet, High-Fat
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