GSE146108: VEGF-B Signaling Impairs Endothelial Glucose Transcytosis via an LDLR-dependent Decrease in Membrane Cholesterol Loading [HBMEC]

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GROUP CONDITION SAMPLES
HBMEC: Human brain microvascular endothelial cell line
GSM4365464 GSM4365465 GSM4365466
GSM4365473 GSM4365474 GSM4365475
GSM4365467 GSM4365468 GSM4365469
GSM4365470 GSM4365471 GSM4365472
GSM4365476 GSM4365477 GSM4365478
Description

Submission Date: Feb 28, 2020

Summary: Regulation of endothelial nutrient transport is poorly understood. Vascular endothelial growth factor (VEGF)-B signaling in endothelial cells promotes uptake and transcytosis of fatty acids (FA) from the bloodstream to the underlying tissue, advancing pathological lipid accumulation and lipotoxicity in diabetic complications. Here we demonstrate a VEGF-B dependent obstruction of endothelial glucose transport attributed to plasma membrane lipid alterations affecting glucose transporter 1 function, which was independent of FA uptake. Specifically, VEGF-B signaling impaired recycling of low-density lipoprotein receptor to the plasma membrane, leading to reduced cholesterol uptake and membrane cholesterol loading, decreasing endothelial glucose uptake capacity. Inhibiting VEGF-B in vivo was accordingly linked to reconstitution of membrane cholesterol and induction of glucose uptake, of particular relevance for conditions inferring insulin resistance and diabetic complications. In summary, our study reveals a novel mechanism of action for VEGF-B in endothelial nutrient uptake and highlights the impact of membrane cholesterol for the regulation of endothelial glucose transport.

GEO Accession ID: GSE146108

PMID: 32449307

Description

Submission Date: Feb 28, 2020

Summary: Regulation of endothelial nutrient transport is poorly understood. Vascular endothelial growth factor (VEGF)-B signaling in endothelial cells promotes uptake and transcytosis of fatty acids (FA) from the bloodstream to the underlying tissue, advancing pathological lipid accumulation and lipotoxicity in diabetic complications. Here we demonstrate a VEGF-B dependent obstruction of endothelial glucose transport attributed to plasma membrane lipid alterations affecting glucose transporter 1 function, which was independent of FA uptake. Specifically, VEGF-B signaling impaired recycling of low-density lipoprotein receptor to the plasma membrane, leading to reduced cholesterol uptake and membrane cholesterol loading, decreasing endothelial glucose uptake capacity. Inhibiting VEGF-B in vivo was accordingly linked to reconstitution of membrane cholesterol and induction of glucose uptake, of particular relevance for conditions inferring insulin resistance and diabetic complications. In summary, our study reveals a novel mechanism of action for VEGF-B in endothelial nutrient uptake and highlights the impact of membrane cholesterol for the regulation of endothelial glucose transport.

GEO Accession ID: GSE146108

PMID: 32449307

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