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 ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
---|---|---|---|---|---|---|---|---|
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)* |