Endothelial cell CD36 regulates membrane ceramide formation, exosome fatty acid transfer and circulating fatty acid levels
Abstract Endothelial cell (EC) CD36 controls tissue fatty acid (FA) uptake. Here we examine how ECs transfer FAs. FA interaction with apical membrane CD36 induces Src phosphorylation of caveolin-1 tyrosine-14 (Cav-1Y14) and ceramide generation in caveolae. Ensuing fission of caveolae yields vesicles...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-39752-3 |
| _version_ | 1797784560530882560 |
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| author | V. S. Peche T. A. Pietka M. Jacome-Sosa D. Samovski H. Palacios G. Chatterjee-Basu A. C. Dudley W. Beatty G. A. Meyer I. J. Goldberg N. A. Abumrad |
| author_facet | V. S. Peche T. A. Pietka M. Jacome-Sosa D. Samovski H. Palacios G. Chatterjee-Basu A. C. Dudley W. Beatty G. A. Meyer I. J. Goldberg N. A. Abumrad |
| author_sort | V. S. Peche |
| collection | DOAJ |
| description | Abstract Endothelial cell (EC) CD36 controls tissue fatty acid (FA) uptake. Here we examine how ECs transfer FAs. FA interaction with apical membrane CD36 induces Src phosphorylation of caveolin-1 tyrosine-14 (Cav-1Y14) and ceramide generation in caveolae. Ensuing fission of caveolae yields vesicles containing FAs, CD36 and ceramide that are secreted basolaterally as small (80–100 nm) exosome-like extracellular vesicles (sEVs). We visualize in transwells EC transfer of FAs in sEVs to underlying myotubes. In mice with EC-expression of the exosome marker emeraldGFP-CD63, muscle fibers accumulate circulating FAs in emGFP-labeled puncta. The FA-sEV pathway is 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 reduces muscle FA uptake, raises circulating FAs, which remain in blood vessels, and lowers glucose, mimicking prominent Cd36 −/− mice phenotypes. The findings show that FA uptake influences membrane ceramide, endocytosis, and EC communication with parenchymal cells. |
| first_indexed | 2024-03-13T00:41:38Z |
| format | Article |
| id | doaj.art-6f251f202667484391582bbdd86d20a1 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-13T00:41:38Z |
| publishDate | 2023-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-6f251f202667484391582bbdd86d20a12023-07-09T11:18:13ZengNature PortfolioNature Communications2041-17232023-07-0114111910.1038/s41467-023-39752-3Endothelial cell CD36 regulates membrane ceramide formation, exosome fatty acid transfer and circulating fatty acid levelsV. S. Peche0T. A. Pietka1M. Jacome-Sosa2D. Samovski3H. Palacios4G. Chatterjee-Basu5A. C. Dudley6W. Beatty7G. A. Meyer8I. J. Goldberg9N. A. Abumrad10Department of Medicine, Division of Nutritional Sciences, Washington University School of MedicineDepartment of Medicine, Division of Nutritional Sciences, Washington University School of MedicineDepartment of Medicine, Division of Nutritional Sciences, Washington University School of MedicineDepartment of Medicine, Division of Nutritional Sciences, Washington University School of MedicineDepartment of Medicine, Division of Nutritional Sciences, Washington University School of MedicineDepartment of Medicine, Division of Nutritional Sciences, Washington University School of MedicineDepartment of Microbiology, Immunology, and Cancer Biology, University of VirginiaDepartment of Microbiology, Washington University School of MedicineDepartments of Physical Therapy, Neurology and Orthopedic Surgery, Washington University School of MedicineDepartment of Medicine, Division of Endocrinology, Diabetes and Metabolism, New York University Grossman School of MedicineDepartment of Medicine, Division of Nutritional Sciences, Washington University School of MedicineAbstract Endothelial cell (EC) CD36 controls tissue fatty acid (FA) uptake. Here we examine how ECs transfer FAs. FA interaction with apical membrane CD36 induces Src phosphorylation of caveolin-1 tyrosine-14 (Cav-1Y14) and ceramide generation in caveolae. Ensuing fission of caveolae yields vesicles containing FAs, CD36 and ceramide that are secreted basolaterally as small (80–100 nm) exosome-like extracellular vesicles (sEVs). We visualize in transwells EC transfer of FAs in sEVs to underlying myotubes. In mice with EC-expression of the exosome marker emeraldGFP-CD63, muscle fibers accumulate circulating FAs in emGFP-labeled puncta. The FA-sEV pathway is 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 reduces muscle FA uptake, raises circulating FAs, which remain in blood vessels, and lowers glucose, mimicking prominent Cd36 −/− mice phenotypes. The findings show that FA uptake influences membrane ceramide, endocytosis, and EC communication with parenchymal cells.https://doi.org/10.1038/s41467-023-39752-3 |
| spellingShingle | V. S. Peche T. A. Pietka M. Jacome-Sosa D. Samovski H. Palacios G. Chatterjee-Basu A. C. Dudley W. Beatty G. A. Meyer I. J. Goldberg N. A. Abumrad Endothelial cell CD36 regulates membrane ceramide formation, exosome fatty acid transfer and circulating fatty acid levels Nature Communications |
| title | Endothelial cell CD36 regulates membrane ceramide formation, exosome fatty acid transfer and circulating fatty acid levels |
| title_full | Endothelial cell CD36 regulates membrane ceramide formation, exosome fatty acid transfer and circulating fatty acid levels |
| title_fullStr | Endothelial cell CD36 regulates membrane ceramide formation, exosome fatty acid transfer and circulating fatty acid levels |
| title_full_unstemmed | Endothelial cell CD36 regulates membrane ceramide formation, exosome fatty acid transfer and circulating fatty acid levels |
| title_short | Endothelial cell CD36 regulates membrane ceramide formation, exosome fatty acid transfer and circulating fatty acid levels |
| title_sort | endothelial cell cd36 regulates membrane ceramide formation exosome fatty acid transfer and circulating fatty acid levels |
| url | https://doi.org/10.1038/s41467-023-39752-3 |
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