• Image
  • Image
  • Image
  • Image

Lacteal Junction Zippering Protects Against Diet-induced Obesity

Anne Eichmann, Ph.D.

AEphotoregister

Ensign Professor of Medicine (Cardiology)
Yale University
New Haven, CT

November 8, 2018 at 1:00pm EDT

 

 

 

 

 

 

 

Anne Eichmann -

Research in Dr. Eichmann's group concerns the vascular system, its development and contribution to human pathologies. Vascular development accompanies growth of the organism. Endothelial cells that constitute the vascular system proliferate and differentiate at the same rate as the organism grows, to ensure appropriate oxygen and nutriment supply of every tissue and cell in the body. In adults, vascular development becomes quiescent and EC proliferation occurs only in certain physiological situations (menstrual cycle, physical exercise, pregnancy) and pathologies, including diabetes, ageing-associated macular degeneration, atherosclerosis, tissue ischemia (heart, brain, legs) and malignant tumors. Taken together, more than 80 diseases are associated with dysfunctional vessels, accounting for the large majority of deaths in the western world. Identification of the molecular mechanisms responsible for vascular development is thus driven by the need to develop therapeutic agents. The long-term goal of my laboratory is to understand the cellular and molecular mechanisms controlling vascular patterning. We aim to identify key molecular events underlying angiogenesis, lymphangiogenesis and arteriogenesis and to establish the principles governing development of the vertebrate vascular system. Vessel networks are vulnerable to diseases, and abnormal vascular development in cardiovascular disease, cancer and diabetes is the major cause of morbidity and mortality in the developed world. We expect that understanding mechanisms controlling developmental vessel patterning will lead to novel strategies to prevent these diseases.

Presentation - 

The presentation entitled, "Lacteal junction zippering protects against diet-induced obesity," is based on 

Science. 2018 Aug 10;361(6402):599-603. doi: 10.1126/science.aap9331


Lacteal junction zippering protects against diet-induced obesity.
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

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.

If you have a subscription to Science, go to http://science.sciencemag.org/content/361/6402/599/tab-pdf 

Registration - 

Click here to register now!

All participants will be required to register. Current NAVBO members in good standing can register for free, however, the registration form must be completed.  Non-members will be charged a $25 fee for each webinar.  Once registration is complete, each registrant will receive a link and unique pin to join the meeting.  We are using GoToWebinar.  The confirmation email will include information about accessing the webinar.

If you have any questions, please contact This email address is being protected from spambots. You need JavaScript enabled to view it.