Key result
Circulating exosomes express CD36 and increase their lipid content after a high-fat meal, enabling them to take up free fatty acids from the bloodstream and deliver them to cardiac cells.
Why the study?
Regulation of circulating free fatty acid levels and delivery is crucial to maintain tissue homeostasis, prompting investigation into exosome-mediated delivery to cardiac cells.
This study identifies a novel mechanism by which circulating exosomes deliver free fatty acids from the bloodstream to cardiac tissue, a process partially mediated by the CD36 transporter.
May connect systemic FFAs to cardiac cells via exosomes; hypothesis-generating for CD36 as a therapeutic target.
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.
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García et al. (2019) studied Healthy. High caloric breakfast (postprandial state) vs. Overnight fast (fasting state) was evaluated on Lipid content and free fatty acid uptake by circulating exosomes. Circulating exosomes express CD36 and increase their lipid content after a high-fat meal, enabling them to take up free fatty acids from the bloodstream and deliver them to cardiac cells.
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