Endothelial metabolic control of insulin sensitivity through resident macrophages
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Date
2024-11-05
Publication Type
Journal Article
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yes
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Abstract
Endothelial cells (ECs) not only form passive blood conduits but actively contribute to nutrient transport and organ homeostasis. The role of ECs in glucose homeostasis is, however, poorly understood. Here, we show that, in skeletal muscle, endothelial glucose transporter 1 (Glut1/Slc2a1) controls glucose uptake via vascular metabolic control of muscle-resident macrophages without affecting transendothelial glucose transport. Lowering endothelial Glut1 via genetic depletion (Glut1^ΔEC) or upon a short-term high-fat diet increased angiocrine osteopontin (OPN/Spp1) secretion. This promoted resident muscle macrophage activation and proliferation, which impaired muscle insulin sensitivity. Consequently, co-deleting Spp1 from ECs prevented macrophage accumulation and improved insulin sensitivity in Glut1^ΔEC mice. Mechanistically, Glut1-dependent endothelial glucose metabolic rewiring increased OPN in a serine metabolism-dependent fashion. Our data illustrate how the glycolytic endothelium creates a microenvironment that controls resident muscle macrophage phenotype and function and directly links resident muscle macrophages to the maintenance of muscle glucose homeostasis.
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published
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Journal / series
Volume
36 (11)
Pages / Article No.
2383 - 2401000000000
Publisher
Cell Press
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Date collected
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Subject
resident macrophages; endothelial cells; skeletal muscle; insulin sensitivity; osteopontin; vasculature; endothelial metabolism; GLUT1; inflammation; serine
Organisational unit
09560 - De Bock, Katrien / De Bock, Katrien
03596 - Kopf, Manfred (emeritus) / Kopf, Manfred (emeritus)
03819 - Wolfrum, Christian (ehemalig) / Wolfrum, Christian (former)
08839 - Zamboni, Nicola (Tit.-Prof.)
Notes
Funding
208041 - Endothelial metabolism to promote muscle revascularization and regeneration (SNF)