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| Status |
Public on Jul 02, 2023 |
| Title |
Endothelial Cell CD36 Regulates Membrane Ceramide Formation, Exosome Fatty Acid Delivery to Tissues and Circulating Fatty Acid Levels |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Endothelial cell (EC) CD36 controls tissue fatty acid (FA) uptake. Here we examined how ECs transfer FAs. FA interaction with apical membrane CD36 induced Src phosphorylation of caveolin-1 tyrosine-14 (Cav-1Y14) and ceramide generation in caveolae. Fission of the caveolae yielded vesicles containing FAs, CD36 and ceramide that were secreted basolaterally as small (80-100nm) exosome-like extracellular vesicles (sEVs). We visualized EC transfer of FAs in sEVs to underlying myotubes in transwells. In mice with EC-expression of the exosome marker emeraldGFP-CD63, muscle fibers accumulated circulating FAs in emGFP-labeled puncta. The FA-sEV pathway was mapped through its suppression by CD36 depletion, blocking actin-remodeling, Src inhibition, Cav-1Y14 mutation, and neutral sphingomyelinase 2 inhibition. Suppression of sEV formation in mice reduced muscle FA uptake, raised circulating FAs, which remained in blood vessels, and lowered glucose, mimicking prominent Cd36-/- phenotypes. The findings show that FA uptake influences membrane ceramide, endocytosis, and EC communication with parenchymal cells.
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| Overall design |
Gene expression analyses was conducted using RNASeq on control or CD36 knockdown human dermal microvascular cells
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| Contributor(s) |
Abumrad N, Peche V, Pietka T |
| Citation(s) |
37419919 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| R01 DK111175 |
ROLE OF CD36 IN NUTRIENT DELIVERY AND ITS DYSFUNCTION IN AFRICAN AMERICANS |
WASHINGTON UNIVERSITY |
Nada A. Abumrad |
| R01 HL045095 |
Pathways of Tissue Lipid Uptake |
NEW YORK UNIVERSITY SCHOOL OF MEDICINE |
Nada A. Abumrad |
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| Submission date |
Jun 27, 2023 |
| Last update date |
Sep 12, 2023 |
| Contact name |
Nada Abumrad |
| E-mail(s) |
tpietka@dom.wustl.edu, nabumrad@wustl.edu
|
| Organization name |
Washington University
|
| Street address |
660 S. Euclid
|
| City |
St Louis |
| ZIP/Postal code |
63110 |
| Country |
USA |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA988132 |
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