Circulating exosomes deliver free fatty acids from the bloodstream to cardiac cells: Possible role of CD36.
Regulation of circulating free fatty acid (FFA) levels and delivery is crucial to maintain tissue homeostasis. Exosomes are nanomembranous vesicles that are released from diverse cell types and mediate intercellular communication by delivering bioactive molecules. Here, we sought to investigate the...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2019-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0217546 |
| _version_ | 1830515046517571584 |
|---|---|
| author | N A Garcia H González-King E Grueso R Sánchez A Martinez-Romero B Jávega J E O'Connor P J Simons A Handberg P Sepúlveda |
| author_facet | N A Garcia H González-King E Grueso R Sánchez A Martinez-Romero B Jávega J E O'Connor P J Simons A Handberg P Sepúlveda |
| author_sort | N A Garcia |
| collection | DOAJ |
| description | Regulation of circulating free fatty acid (FFA) levels and delivery is crucial to maintain tissue homeostasis. Exosomes are nanomembranous vesicles that are released from diverse cell types and mediate intercellular communication by delivering bioactive molecules. Here, we sought to investigate the uptake of FFAs by circulating exosomes, the delivery of FFA-loaded exosomes to cardiac cells and the possible role of the FFA transporter CD36 in these processes. Circulating exosomes were purified from the serum of healthy donors after an overnight fast (F) or 20 minutes after a high caloric breakfast (postprandial, PP). Western blotting, Immunogold Electron Microscopy and FACS analysis of circulating exosomes showed that CD36 was expressed under both states, but was higher in postprandial-derived exosomes. Flow cytometry analysis showed that circulating exosomes were able to take-up FFA directly from serum. Importantly, preincubation of exosomes with a blocking CD36 antibody significantly impeded uptake of the FFA analogue BODIPY, pointing to the role of CD36 in FFA exosomal uptake. Finally, we found that circulating exosomes could delivery FFA analogue BODIPY into cardiac cells ex vivo and in vivo in a mice model. Overall, our results suggest a novel mechanism in which circulating exosomes can delivery FFAs from the bloodstream to cardiac tissue. Further studies will be necessary to understand this mechanism and, in particular, its potential involvement in metabolic pathologies such as obesity, diabetes and atherosclerosis. |
| first_indexed | 2024-12-22T03:16:15Z |
| format | Article |
| id | doaj.art-9bd75770cd8c4139afbd840df2950796 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T03:16:15Z |
| publishDate | 2019-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-9bd75770cd8c4139afbd840df29507962022-12-21T18:40:50ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-01145e021754610.1371/journal.pone.0217546Circulating exosomes deliver free fatty acids from the bloodstream to cardiac cells: Possible role of CD36.N A GarciaH González-KingE GruesoR SánchezA Martinez-RomeroB JávegaJ E O'ConnorP J SimonsA HandbergP SepúlvedaRegulation of circulating free fatty acid (FFA) levels and delivery is crucial to maintain tissue homeostasis. Exosomes are nanomembranous vesicles that are released from diverse cell types and mediate intercellular communication by delivering bioactive molecules. Here, we sought to investigate the uptake of FFAs by circulating exosomes, the delivery of FFA-loaded exosomes to cardiac cells and the possible role of the FFA transporter CD36 in these processes. Circulating exosomes were purified from the serum of healthy donors after an overnight fast (F) or 20 minutes after a high caloric breakfast (postprandial, PP). Western blotting, Immunogold Electron Microscopy and FACS analysis of circulating exosomes showed that CD36 was expressed under both states, but was higher in postprandial-derived exosomes. Flow cytometry analysis showed that circulating exosomes were able to take-up FFA directly from serum. Importantly, preincubation of exosomes with a blocking CD36 antibody significantly impeded uptake of the FFA analogue BODIPY, pointing to the role of CD36 in FFA exosomal uptake. Finally, we found that circulating exosomes could delivery FFA analogue BODIPY into cardiac cells ex vivo and in vivo in a mice model. Overall, our results suggest a novel mechanism in which circulating exosomes can delivery FFAs from the bloodstream to cardiac tissue. Further studies will be necessary to understand this mechanism and, in particular, its potential involvement in metabolic pathologies such as obesity, diabetes and atherosclerosis.https://doi.org/10.1371/journal.pone.0217546 |
| spellingShingle | N A Garcia H González-King E Grueso R Sánchez A Martinez-Romero B Jávega J E O'Connor P J Simons A Handberg P Sepúlveda Circulating exosomes deliver free fatty acids from the bloodstream to cardiac cells: Possible role of CD36. PLoS ONE |
| title | Circulating exosomes deliver free fatty acids from the bloodstream to cardiac cells: Possible role of CD36. |
| title_full | Circulating exosomes deliver free fatty acids from the bloodstream to cardiac cells: Possible role of CD36. |
| title_fullStr | Circulating exosomes deliver free fatty acids from the bloodstream to cardiac cells: Possible role of CD36. |
| title_full_unstemmed | Circulating exosomes deliver free fatty acids from the bloodstream to cardiac cells: Possible role of CD36. |
| title_short | Circulating exosomes deliver free fatty acids from the bloodstream to cardiac cells: Possible role of CD36. |
| title_sort | circulating exosomes deliver free fatty acids from the bloodstream to cardiac cells possible role of cd36 |
| url | https://doi.org/10.1371/journal.pone.0217546 |
| work_keys_str_mv | AT nagarcia circulatingexosomesdeliverfreefattyacidsfromthebloodstreamtocardiaccellspossibleroleofcd36 AT hgonzalezking circulatingexosomesdeliverfreefattyacidsfromthebloodstreamtocardiaccellspossibleroleofcd36 AT egrueso circulatingexosomesdeliverfreefattyacidsfromthebloodstreamtocardiaccellspossibleroleofcd36 AT rsanchez circulatingexosomesdeliverfreefattyacidsfromthebloodstreamtocardiaccellspossibleroleofcd36 AT amartinezromero circulatingexosomesdeliverfreefattyacidsfromthebloodstreamtocardiaccellspossibleroleofcd36 AT bjavega circulatingexosomesdeliverfreefattyacidsfromthebloodstreamtocardiaccellspossibleroleofcd36 AT jeoconnor circulatingexosomesdeliverfreefattyacidsfromthebloodstreamtocardiaccellspossibleroleofcd36 AT pjsimons circulatingexosomesdeliverfreefattyacidsfromthebloodstreamtocardiaccellspossibleroleofcd36 AT ahandberg circulatingexosomesdeliverfreefattyacidsfromthebloodstreamtocardiaccellspossibleroleofcd36 AT psepulveda circulatingexosomesdeliverfreefattyacidsfromthebloodstreamtocardiaccellspossibleroleofcd36 |