Alexandre Gallerand, Bastien Dolfi, Marion I. Stunault, Zakariya Caillot, Alexia Castiglione, Axelle Strazzulla, Chuqiao Chen, Gyu Seong Heo, Hannah Luehmann, Flora Batoul, Nathalie Vaillant, Adélie Dumont, Thomas Pilot, Johanna Merlin, Fairouz N. Zair, Jerome Gilleron, Adeline Bertola, Peter Carmeliet, Jesse W. Williams, Rafael J. Arguello, David Masson, David Dombrowicz, Laurent Yvan-Charvet, Denis Doyen, Arvand Haschemi, Yongjian Liu, Rodolphe R. Guinamard, Stoyan Ivanov
{"title":"Glucose metabolism controls monocyte homeostasis and migration but has no impact on atherosclerosis development in mice","authors":"Alexandre Gallerand, Bastien Dolfi, Marion I. Stunault, Zakariya Caillot, Alexia Castiglione, Axelle Strazzulla, Chuqiao Chen, Gyu Seong Heo, Hannah Luehmann, Flora Batoul, Nathalie Vaillant, Adélie Dumont, Thomas Pilot, Johanna Merlin, Fairouz N. Zair, Jerome Gilleron, Adeline Bertola, Peter Carmeliet, Jesse W. Williams, Rafael J. Arguello, David Masson, David Dombrowicz, Laurent Yvan-Charvet, Denis Doyen, Arvand Haschemi, Yongjian Liu, Rodolphe R. Guinamard, Stoyan Ivanov","doi":"10.1038/s41467-024-53267-5","DOIUrl":null,"url":null,"abstract":"<p>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.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":null,"pages":null},"PeriodicalIF":14.7000,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Communications","FirstCategoryId":"103","ListUrlMain":"https://doi.org/10.1038/s41467-024-53267-5","RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}
引用次数: 0
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.
期刊介绍:
Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.