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Visceral obesity and insulin resistance associate with CD36 deletion in lymphatic endothelial cells

Author

Listed:
  • Vincenza Cifarelli

    (Washington University School of Medicine)

  • Sila Appak-Baskoy

    (Heidelberg University
    German Cancer Research Center (DKFZ-ZMBH Alliance))

  • Vivek S. Peche

    (Washington University School of Medicine)

  • Andrew Kluzak

    (Washington University School of Medicine)

  • Trevor Shew

    (Washington University School of Medicine)

  • Ramkumar Narendran

    (Washington University School of Medicine)

  • Kathryn M. Pietka

    (Washington University School of Medicine)

  • Marina Cella

    (Washington University School of Medicine)

  • Curtis W. Walls

    (Washington University School of Medicine)

  • Rafael Czepielewski

    (Washington University School of Medicine)

  • Stoyan Ivanov

    (Washington University School of Medicine)

  • Gwendalyn J. Randolph

    (Washington University School of Medicine)

  • Hellmut G. Augustin

    (Heidelberg University
    German Cancer Research Center (DKFZ-ZMBH Alliance))

  • Nada A. Abumrad

    (Washington University School of Medicine
    Washington University School of Medicine)

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 (Cd36ΔLEC) increases discontinuity of LEC VE-cadherin junctions in lacteals and collecting vessels. Cd36ΔLEC 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.

Suggested Citation

  • Vincenza Cifarelli & Sila Appak-Baskoy & Vivek S. Peche & Andrew Kluzak & Trevor Shew & Ramkumar Narendran & Kathryn M. Pietka & Marina Cella & Curtis W. Walls & Rafael Czepielewski & Stoyan Ivanov & , 2021. "Visceral obesity and insulin resistance associate with CD36 deletion in lymphatic endothelial cells," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23808-3
    DOI: 10.1038/s41467-021-23808-3
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    Cited by:

    1. Nieves Montenegro-Navarro & Claudia García-Báez & Melissa García-Caballero, 2023. "Molecular and metabolic orchestration of the lymphatic vasculature in physiology and pathology," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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