Contributors: Laboratoire de PhysioMédecine Moléculaire (LP2M); Université Nice Sophia Antipolis (1965 - 2019) (UNS)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UniCA); Centre méditerranéen de médecine moléculaire (C3M); Université Nice Sophia Antipolis (1965 - 2019) (UNS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UniCA); Université médicale de Vienne, Autriche; Washington University School of Medicine in St. Louis; Washington University in Saint Louis (WUSTL); Center for Translational and Molecular medicine Dijon - UMR1231 (CTM); École Pratique des Hautes Études (EPHE); Université Paris Sciences et Lettres (PSL)-Université Paris Sciences et Lettres (PSL)-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon; Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro); Laboratory of Angiogenesis and Vascular Metabolism Leuven, Belgium (VIB-CCB); Department of Oncology Leuven, Belgium; Catholic University of Leuven = Katholieke Universiteit Leuven (KU Leuven)-Catholic University of Leuven = Katholieke Universiteit Leuven (KU Leuven); University of Minnesota Medical School; University of Minnesota System (UMN); Centre National de la Recherche Scientifique (CNRS); Institut National de la Santé et de la Recherche Médicale (INSERM); Aix Marseille Université (AMU); Centre d'Immunologie de Marseille - Luminy (CIML); Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS); Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 (RNMCD); Institut Pasteur de Lille; Pasteur Network (Réseau International des Instituts Pasteur)-Pasteur Network (Réseau International des Instituts Pasteur)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire CHU Lille (CHRU Lille); Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U 1011 (RNMCD); Hôpital Pasteur Nice (CHU); Medizinische Universität Wien = Medical University of Vienna; Washington University School of Medicine Saint Louis, MO; ANR-17-CE14-0017,MOTACARD,Ciblage des voies cardiométaboliques pour rétablir l'horloge biologique des monocytes(2017); ANR-19-ECVD-0005,MyPenPath,The Role of the Pentose Phosphate Pathway on Myeloid Cells Functions during Atherosclerosis(2019); ANR-15-IDEX-0001,UCA JEDI,Idex UCA JEDI(2015)
Abstract: International audience ; 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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