Fiche publication
Date publication
octobre 2024
Journal
Nature communications
Auteurs
Membres identifiés du Cancéropôle Est :
Pr MASSON David
Tous les auteurs :
Gallerand A, Dolfi B, Stunault MI, Caillot Z, Castiglione A, Strazzulla A, Chen C, Heo GS, Luehmann H, Batoul F, Vaillant N, Dumont A, Pilot T, Merlin J, Zair FN, Gilleron J, Bertola A, Carmeliet P, Williams JW, Arguello RJ, Masson D, Dombrowicz D, Yvan-Charvet L, Doyen D, Haschemi A, Liu Y, Guinamard RR, Ivanov S
Lien Pubmed
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.
Mots clés
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
Référence
Nat Commun. 2024 10 19;15(1):9027
