Summary of project PR001617

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001617. The data can be accessed directly via it's Project DOI: 10.21228/M8PH89 This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

Project ID: PR001617
Project DOI:doi: 10.21228/M8PH89
Project Title:Endothelial Cell CD36 Regulates Membrane Ceramide Formation, Exosome Fatty Acid Delivery to Tissues and Circulating Fatty Acid Levels
Project Type:MS quantitative analysis
Project Summary:Endothelial cell (EC) CD36 controls tissue fatty acid (FA) uptake. Here we visualized FA transfer by ECs using click chemistry. Apical FA interaction with EC CD36 induces actin reorganization, caveolin-1 tyrosine 14 (Cav-1Y14) phosphorylation, and ceramide generation in caveolae, culminating in caveolae internalization into FA/CD36/ceramide vesicles that are secreted basolaterally as small extracellular vesicles, sEVs (exosomes). In transwells, ECs expressing fluorescent CD63 (exosomal marker) transfer FAs to underlying myotubes in CD63-labeled sEVs. In vivo FA-CD63-CD36 transfer from ECs to muscle is shown using a mouse with EC-specific expression of emGFP-CD63. CD36 depletion, actin-binding latrunculin-B, Src inhibition, Cav-1Y14 mutation, and membrane neutral sphingomyelinase inhibition by GW4869 helped map the FA-sEV pathway. Injecting GW4869 to mice reduced muscle FA uptake, raised plasma FAs and lowered glucose, mimicking prominent Cd36-/- phenotypes. The FA-sEV pathway we describe contributes to crosstalk between ECs and underlying cells and links regulation of membrane ceramide to blood FAs.
Institute:Washington University in St. Louis
Department:IM-Nutitrional Science
Laboratory:Abumrad Lab
Last Name:Palacios
First Name:Hector
Address:West Building 00201, St. Louis, Missouri, 63110, USA
Email:hectorp@wustl.edu
Phone:314-362-5397

Summary of all studies in project PR001617

Study IDStudy TitleSpeciesInstituteAnalysis
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ST002503 Endothelial Cell CD36 Regulates Membrane Ceramide Formation, Exosome Fatty Acid Delivery to Tissues and Circulating Fatty Acid Levels Mus musculus Washington University in St. Louis MS 2023-03-22 1 48 Uploaded data (542M)*
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