Summary of Study ST002503
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
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
Study ID | ST002503 |
Study Title | Endothelial Cell CD36 Regulates Membrane Ceramide Formation, Exosome Fatty Acid Delivery to Tissues and Circulating Fatty Acid Levels |
Study Type | Membrane ceramide and Fatty Acid Uptake |
Study 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 |
hectorp@wustl.edu | |
Phone | 314-362-5397 |
Submit Date | 2023-03-06 |
Raw Data Available | Yes |
Raw Data File Type(s) | mzML |
Analysis Type Detail | LC-MS |
Release Date | 2023-03-22 |
Release Version | 1 |
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Treatment:
Treatment ID: | TR002612 |
Treatment Summary: | Myotube Treatment with hMEC Generated FA-sEV: hMECs grown to confluence were serum-starved and treated with OA:BSA (100µM:50µM) or BSA (50µM controls). The sEVs were isolated from media collected over 48h and particle number and protein content determined. |