Regulation of endothelial nutrient transport is poorly understood. Vascular endothelial growth factor B (VEGF‐B) signaling in endothelial cells promotes uptake and transcytosis of fatty acids from the bloodstream to the underlying tissue, advancing pathological lipid accumulation and lipotoxicity in diabetic complications. Here, we demonstrate that VEGF‐B limits endothelial glucose transport independent of fatty acid uptake. Specifically, VEGF‐B signaling impairs recycling of low‐density lipoprotein receptor (LDLR) to the plasma membrane, leading to reduced cholesterol uptake and membrane cholesterol loading. Reduced cholesterol levels in the membrane leads to a decrease in glucose transporter 1 (GLUT1)‐dependent endothelial glucose uptake. Inhibiting VEGF‐B in vivo reconstitutes membrane cholesterol levels and restores glucose uptake, which is of particular relevance for conditions involving insulin resistance and diabetic complications. In summary, our study reveals a mechanism whereby VEGF‐B regulates endothelial nutrient uptake and highlights the impact of membrane cholesterol for regulation of endothelial glucose transport.

中文翻译：

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VEGF-B信号传导通过降低膜胆固醇含量而损害内皮葡萄糖的胞吞作用。

对内皮营养运输的调控了解甚少。内皮细胞中的血管内皮生长因子B（VEGF-B）信号传导促进脂肪酸从血流到基础组织的吸收和胞吞，在糖尿病并发症中促进病理性脂质蓄积和脂毒性。在这里，我们证明VEGF-B限制了内皮葡萄糖的转运，而与脂肪酸的摄取无关。具体而言，VEGF-B信号传导会损害低密度脂蛋白受体（LDLR）向质膜的再循环，从而降低胆固醇摄取和膜胆固醇负荷。膜中胆固醇水平的降低导致葡萄糖转运蛋白1（GLUT1）依赖性内皮葡萄糖摄取的减少。体内抑制VEGF-B重组膜胆固醇水平并恢复葡萄糖摄取，这与涉及胰岛素抵抗和糖尿病并发症的疾病特别相关。总而言之，我们的研究揭示了VEGF-B调节内皮营养摄入的机制，并强调了膜胆固醇对调节内皮糖运输的影响。