Macrophage-derived glutamine boosts satellite cells and muscle regeneration.

Details

Serval ID
serval:BIB_3434B6E6C298
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Macrophage-derived glutamine boosts satellite cells and muscle regeneration.
Journal
Nature
Author(s)
Shang M., Cappellesso F., Amorim R., Serneels J., Virga F., Eelen G., Carobbio S., Rincon M.Y., Maechler P., De Bock K., Ho P.C., Sandri M., Ghesquière B., Carmeliet P., Di Matteo M., Berardi E., Mazzone M.
ISSN
1476-4687 (Electronic)
ISSN-L
0028-0836
Publication state
In Press
Peer-reviewed
Oui
Language
english
Notes
Publication types: Journal Article
Publication Status: aheadofprint
Abstract
Muscle regeneration is sustained by infiltrating macrophages and the consequent activation of satellite cells <sup>1-4</sup> . Macrophages and satellite cells communicate in different ways <sup>1-5</sup> , but their metabolic interplay has not been investigated. Here we show, in a mouse model, that muscle injuries and ageing are characterized by intra-tissue restrictions of glutamine. Low levels of glutamine endow macrophages with the metabolic ability to secrete glutamine via enhanced glutamine synthetase (GS) activity, at the expense of glutamine oxidation mediated by glutamate dehydrogenase 1 (GLUD1). Glud1-knockout macrophages display constitutively high GS activity, which prevents glutamine shortages. The uptake of macrophage-derived glutamine by satellite cells through the glutamine transporter SLC1A5 activates mTOR and promotes the proliferation and differentiation of satellite cells. Consequently, macrophage-specific deletion or pharmacological inhibition of GLUD1 improves muscle regeneration and functional recovery in response to acute injury, ischaemia or ageing. Conversely, SLC1A5 blockade in satellite cells or GS inactivation in macrophages negatively affects satellite cell functions and muscle regeneration. These results highlight the metabolic crosstalk between satellite cells and macrophages, in which macrophage-derived glutamine sustains the functions of satellite cells. Thus, the targeting of GLUD1 may offer therapeutic opportunities for the regeneration of injured or aged muscles.
Pubmed
Web of science
Create date
10/11/2020 8:44
Last modification date
13/11/2020 6:26
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