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| Status |
Public on Apr 06, 2020 |
| Title |
VEGF-B Signaling Impairs Endothelial Glucose Transcytosis via an LDLR-dependent Decrease in Membrane Cholesterol Loading [HBMEC] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| 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.
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| Overall design |
15 samples; n = 3 per treatment group, 5 treatments
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| |
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| Contributor(s) |
Moessinger C, Nilsson I, Muhl L, Zeitelhofer M, Heller Sahlgren B, Skogsberg J, Eriksson U |
| Citation(s) |
32449307 |
| |
| Submission date |
Feb 28, 2020 |
| Last update date |
Jul 06, 2020 |
| Contact name |
Lars Muhl |
| E-mail(s) |
lars.muhl@ki.se
|
| Organization name |
Karolinska Institutet
|
| Department |
MedH
|
| Lab |
Betsholtz
|
| Street address |
Blickagången 6
|
| City |
Huddinge |
| ZIP/Postal code |
14157 |
| Country |
Sweden |
| |
|
| Platforms (1) |
| GPL6244 |
[HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array [transcript (gene) version] |
|
| Samples (15)
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| This SubSeries is part of SuperSeries: |
| GSE146109 |
VEGF-B Signaling Impairs Endothelial Glucose Transcytosis via an LDLR-dependent Decrease in Membrane Cholesterol Loading |
|
| Relations |
| BioProject |
PRJNA609314 |
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