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

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.

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Publication Details

Journal
Nature Communications
Published
2024-10-18
DOI
https://doi.org/10.1038/s41467-024-53267-5
Citations
10
Primary Topic
Immune cells in cancer
Type
article
Field-Weighted Citation Impact
2.40

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article

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

David Dombrowicz, Johanna Merlin, Nathalie Vaillant, Hannah Luehmann et al.
10 citations
Nature Communications
Immune cells in cancer
2.40
article

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

David Dombrowicz, Johanna Merlin, Nathalie Vaillant, Hannah Luehmann, Marion I. Stunault, Bastien Dolfi, Rafael J. Argüello, Rodolphe Guinamard, Stoyan Ivanov, Chuqiao Chen, Thomas Pilot, Laurent Yvan‐Charvet, Arvand Haschemi, Peter Carmeliet, Alexia Castiglione, Jérôme Gilleron, Alexandre Gallerand, David Masson, Gyu Seong Heo, Adeline Bertola, Zakariya Caillot, Fairouz N. Zair, Yongjian Liu, Jesse W. Williams, Axelle Strazzulla, Adélie Dumont, Flora Batoul, Denis Doyen
article en
10 citations

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.

Nature CommunicationsVol. 15(1)
Centre National de la Recherche Scientifique (FR), Inserm (FR), Université de Bourgogne (FR), Université Côte d'Azur (FR), Washington University in St. Louis (US), Aix-Marseille Université (FR), Institut Pasteur de Lille (FR), Centre Hospitalier Universitaire de Lille (FR), Centre Hospitalier Universitaire de Nice (FR), Laboratoire de PhysioMédecine Moléculaire (FR), VIB-KU Leuven Center for Cancer Biology (BE), Laboratoire Jean-Alexandre Dieudonné (FR), Université Bourgogne Franche-Comté (FR), Centre Méditerranéen de Médecine Moléculaire (FR), University of Minnesota Medical Center (US), Hôpital Pasteur (FR), Centre d’Immunologie de Marseille-Luminy (FR), Medical University of Vienna (AT)
Infrastructures en Biologie Santé et Agronomie, Agence Nationale de la Recherche, Institut National de la Santé et de la Recherche Médicale, Austrian Science Fund, Fondation pour la Recherche Médicale, Fondation de France, European Research Area Network on Cardiovascular Diseases
Openalex Percentile: Top 11%
Immune cells in cancer
2.40
DOIOpen Access PDFOpenAlex
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