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

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

  • Nat Commun. 2024 Oct 19;15(1):9027. doi: 10.1038/s41467-024-53267-5.
Alexandre Gallerand 1 2,  Bastien Dolfi 3 4,  Marion I Stunault 4,  Zakariya Caillot 3,  Alexia Castiglione 3 4,  Axelle Strazzulla 3,  Chuqiao Chen 5,  Gyu Seong Heo 6,  Hannah Luehmann 6,  Flora Batoul 4,  Nathalie Vaillant 4,  Adélie Dumont 4,  Thomas Pilot 7,  Johanna Merlin 4,  Fairouz N Zair 3,  Jerome Gilleron 4,  Adeline Bertola 3,  Peter Carmeliet 8,  Jesse W Williams 9,  Rafael J Arguello 10,  David Masson 7,  David Dombrowicz 11,  Laurent Yvan-Charvet 4,  Denis Doyen 3 12,  Arvand Haschemi 5,  Yongjian Liu 6,  Rodolphe R Guinamard 3 4,  Stoyan Ivanov 13 14
Affiliations

Affiliations

  • 1 Université Côte d'Azur, CNRS, LP2M, Nice, France. Alexandre.gallerand@univ-cotedazur.fr.
  • 2 Université Côte d'Azur, INSERM, C3M, Nice, France. Alexandre.gallerand@univ-cotedazur.fr.
  • 3 Université Côte d'Azur, CNRS, LP2M, Nice, France.
  • 4 Université Côte d'Azur, INSERM, C3M, Nice, France.
  • 5 Department of Laboratory Medicine, Medical University of Vienna, 1090, Vienna, Austria.
  • 6 Department of Radiology, Washington University School of Medicine, Saint Louis, MO, USA.
  • 7 Université Bourgogne Franche-Comté, LNC UMR1231, F-21000, Dijon, France.
  • 8 Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), VIB, Department of Oncology, Leuven Cancer Institute (LKI), KU Leuven, Leuven, 3000, Belgium.
  • 9 Center for Immunology, Department of Integrative Biology and Physiology, University of Minnesota Medical School, Minneapolis, MN, USA.
  • 10 Aix Marseille University, CNRS, INSERM, CIML, Centre d'Immunologie de Marseille-Luminy, Marseille, France.
  • 11 Univ.Lille, INSERM, CHU Lille, Institut Pasteur de Lille, U1011-EGID, 59000, Lille, France.
  • 12 Médecine Intensive Réanimation, Hôpital Pasteur, CHU de Nice, Nice, France.
  • 13 Université Côte d'Azur, CNRS, LP2M, Nice, France. Stoyan.IVANOV@univ-cotedazur.fr.
  • 14 Université Côte d'Azur, INSERM, C3M, Nice, France. Stoyan.IVANOV@univ-cotedazur.fr.
PMID: 39424804 DOI: 10.1038/s41467-024-53267-5
Abstract

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.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-100017
    99.67%, GLUT1抑制剂
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