Glucose metabolism controls monocyte homeostasis and migration but has no impact on atherosclerosis development in mice.


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
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

9027

Subventions

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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Auteurs

Alexandre Gallerand (A)

Université Côte d'Azur, CNRS, LP2M, Nice, France. Alexandre.gallerand@univ-cotedazur.fr.
Université Côte d'Azur, INSERM, C3M, Nice, France. Alexandre.gallerand@univ-cotedazur.fr.

Bastien Dolfi (B)

Université Côte d'Azur, CNRS, LP2M, Nice, France.
Université Côte d'Azur, INSERM, C3M, Nice, France.

Marion I Stunault (MI)

Université Côte d'Azur, INSERM, C3M, Nice, France.

Zakariya Caillot (Z)

Université Côte d'Azur, CNRS, LP2M, Nice, France.

Alexia Castiglione (A)

Université Côte d'Azur, CNRS, LP2M, Nice, France.
Université Côte d'Azur, INSERM, C3M, Nice, France.

Axelle Strazzulla (A)

Université Côte d'Azur, CNRS, LP2M, Nice, France.

Chuqiao Chen (C)

Department of Laboratory Medicine, Medical University of Vienna, 1090, Vienna, Austria.

Gyu Seong Heo (GS)

Department of Radiology, Washington University School of Medicine, Saint Louis, MO, USA.

Hannah Luehmann (H)

Department of Radiology, Washington University School of Medicine, Saint Louis, MO, USA.

Flora Batoul (F)

Université Côte d'Azur, INSERM, C3M, Nice, France.

Nathalie Vaillant (N)

Université Côte d'Azur, INSERM, C3M, Nice, France.

Adélie Dumont (A)

Université Côte d'Azur, INSERM, C3M, Nice, France.

Thomas Pilot (T)

Université Bourgogne Franche-Comté, LNC UMR1231, F-21000, Dijon, France.

Johanna Merlin (J)

Université Côte d'Azur, INSERM, C3M, Nice, France.

Fairouz N Zair (FN)

Université Côte d'Azur, CNRS, LP2M, Nice, France.

Jerome Gilleron (J)

Université Côte d'Azur, INSERM, C3M, Nice, France.

Adeline Bertola (A)

Université Côte d'Azur, CNRS, LP2M, Nice, France.

Peter Carmeliet (P)

Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), VIB, Department of Oncology, Leuven Cancer Institute (LKI), KU Leuven, Leuven, 3000, Belgium.

Jesse W Williams (JW)

Center for Immunology, Department of Integrative Biology and Physiology, University of Minnesota Medical School, Minneapolis, MN, USA.

Rafael J Arguello (RJ)

Aix Marseille University, CNRS, INSERM, CIML, Centre d'Immunologie de Marseille-Luminy, Marseille, France.

David Masson (D)

Université Bourgogne Franche-Comté, LNC UMR1231, F-21000, Dijon, France.

David Dombrowicz (D)

Univ.Lille, INSERM, CHU Lille, Institut Pasteur de Lille, U1011-EGID, 59000, Lille, France.

Laurent Yvan-Charvet (L)

Université Côte d'Azur, INSERM, C3M, Nice, France.

Denis Doyen (D)

Université Côte d'Azur, CNRS, LP2M, Nice, France.
Médecine Intensive Réanimation, Hôpital Pasteur, CHU de Nice, Nice, France.

Arvand Haschemi (A)

Department of Laboratory Medicine, Medical University of Vienna, 1090, Vienna, Austria.

Yongjian Liu (Y)

Department of Radiology, Washington University School of Medicine, Saint Louis, MO, USA.

Rodolphe R Guinamard (RR)

Université Côte d'Azur, CNRS, LP2M, Nice, France.
Université Côte d'Azur, INSERM, C3M, Nice, France.

Stoyan Ivanov (S)

Université Côte d'Azur, CNRS, LP2M, Nice, France. Stoyan.IVANOV@univ-cotedazur.fr.
Université Côte d'Azur, INSERM, C3M, Nice, France. Stoyan.IVANOV@univ-cotedazur.fr.

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