Glucose metabolism controls monocyte homeostasis and migration but has no impact on atherosclerosis development in mice.
Animals
Monocytes
/ metabolism
Atherosclerosis
/ metabolism
Glucose Transporter Type 1
/ metabolism
Cell Movement
Homeostasis
Glucose
/ metabolism
Mice
Receptors, CCR2
/ metabolism
Mice, Inbred C57BL
Male
Plaque, Atherosclerotic
/ metabolism
Glycolysis
Blood Glucose
/ metabolism
Disease Models, Animal
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
19 Oct 2024
19 Oct 2024
Historique:
received:
05
12
2023
accepted:
08
10
2024
medline:
19
10
2024
pubmed:
19
10
2024
entrez:
18
10
2024
Statut:
epublish
Résumé
Monocytes directly contribute to atherosclerosis development by their recruitment to plaques in which they differentiate into macrophages. In the present study, we ask how modulating monocyte glucose metabolism could affect their homeostasis and their impact on atherosclerosis. Here we investigate how circulating metabolites control monocyte behavior in blood, bone marrow and peripheral tissues of mice. We find that serum glucose concentrations correlate with monocyte numbers. In diet-restricted mice, monocytes fail to metabolically reprogram from glycolysis to fatty acid oxidation, leading to reduced monocyte numbers in the blood. Mechanistically, Glut1-dependent glucose metabolism helps maintain CD115 membrane expression on monocytes and their progenitors, and regulates monocyte migratory capacity by modulating CCR2 expression. Results from genetic models and pharmacological inhibitors further depict the relative contribution of different metabolic pathways to the regulation of CD115 and CCR2 expression. Meanwhile, Glut1 inhibition does not impact atherosclerotic plaque development in mouse models despite dramatically reducing blood monocyte numbers, potentially due to the remaining monocytes having increased migratory capacity. Together, these data emphasize the role of glucose uptake and intracellular glucose metabolism in controlling monocyte homeostasis and functions.
Identifiants
pubmed: 39424804
doi: 10.1038/s41467-024-53267-5
pii: 10.1038/s41467-024-53267-5
doi:
Substances chimiques
Glucose Transporter Type 1
0
Glucose
IY9XDZ35W2
Slc2a1 protein, mouse
0
Receptors, CCR2
0
Ccr2 protein, mouse
0
Blood Glucose
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
9027Subventions
Organisme : Agence Nationale de la Recherche (French National Research Agency)
ID : ANR-17-CE14-0017-01
Organisme : Agence Nationale de la Recherche (French National Research Agency)
ID : ANR-15-IDEX-01
Organisme : Austrian Science Fund (Fonds zur Förderung der Wissenschaftlichen Forschung)
ID : I 4646
Organisme : Fondation pour la Recherche Médicale (Foundation for Medical Research in France)
ID : EQU202303016719
Informations de copyright
© 2024. The Author(s).
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