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Vascular endothelial growth factor B controls endothelial fatty acid uptake

Eriksson, Ulf ; Hagberg, Carolina E ; Falkevall, Annelie ; Wang, Xun ; Larsson, Erik ; Huusko, Jenni ; Nilsson, Ingrid ; van Meeteren, Laurens A ; Samen, Erik ; Lu, Li ; Vanwildemeersch, Maarten ; Klar, Joakim ; Genove, Guillem ; Pietras, Kristian ; Stone-Elander, Sharon ; Claesson-Welsh, Lena ; Ylä-Herttuala, Seppo ; Lindahl, Per

Nature (London), 2010-04, Vol.464 (7290), p.917-921 [Periódico revisado por pares]

London: Nature Publishing Group

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Vascular endothelial growth factor B controls endothelial fatty acid uptake
Autor: Eriksson, Ulf ; Hagberg, Carolina E ; Falkevall, Annelie ; Wang, Xun ; Larsson, Erik ; Huusko, Jenni ; Nilsson, Ingrid ; van Meeteren, Laurens A ; Samen, Erik ; Lu, Li ; Vanwildemeersch, Maarten ; Klar, Joakim ; Genove, Guillem ; Pietras, Kristian ; Stone-Elander, Sharon ; Claesson-Welsh, Lena ; Ylä-Herttuala, Seppo ; Lindahl, Per
Assuntos: Adipose Tissue, Brown - metabolism ; Adipose Tissue, White - metabolism ; Animals ; Binding sites ; Biochemistry and Molecular Biology ; Biokemi och molekylärbiologi ; Biological and medical sciences ; Biological Transport ; Cardiovascular diseases ; Care and treatment ; Cell and Molecular Biology ; Cell Biology ; Cell Line ; Cell Nucleus - genetics ; Cell- och molekylärbiologi ; Cellbiologi ; Cells, Cultured ; Dermatologi och venerologi, klinisk genetik, invärtesmedicin ; Dermatology and venerology,clinical genetics, internal medicine ; Diabetes ; Endothelium - cytology ; Endothelium - metabolism ; Fatty Acid Transport Proteins - genetics ; Fatty Acids - metabolism ; Fundamental and applied biological sciences. Psychology ; Gene Expression Regulation ; Genetic aspects ; Genetics ; Genetik ; Humans ; Internal medicine ; Invärtesmedicin ; Male ; MEDICIN ; Medicin och hälsovetenskap ; MEDICINE ; Mice ; Mice, Inbred C57BL ; Mitochondria - genetics ; Mitochondria - metabolism ; Mitochondrial Proteins - genetics ; Mitochondrial Proteins - metabolism ; Molecular and cellular biology ; Molecular medicine (genetics and pathology) ; Molekylär medicin (genetik och patologi) ; Muscles - metabolism ; Myocardium - metabolism ; Neuropilin-1 - genetics ; Neuropilin-1 - metabolism ; Oligonucleotide Array Sequence Analysis ; Organ Specificity ; Physiological aspects ; Proteins ; Rodents ; Signal Transduction ; Transcription, Genetic ; Vascular endothelial growth factor ; Vascular Endothelial Growth Factor B - deficiency ; Vascular Endothelial Growth Factor B - genetics ; Vascular Endothelial Growth Factor B - metabolism ; Vascular Endothelial Growth Factor Receptor-1 - metabolism
É parte de: Nature (London), 2010-04, Vol.464 (7290), p.917-921
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
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Descrição: The vascular endothelial growth factors (VEGFs) are major angiogenic regulators and are involved in several aspects of endothelial cell physiology. However, the detailed role of VEGF-B in blood vessel function has remained unclear. Here we show that VEGF-B has an unexpected role in endothelial targeting of lipids to peripheral tissues. Dietary lipids present in circulation have to be transported through the vascular endothelium to be metabolized by tissue cells, a mechanism that is poorly understood. Bioinformatic analysis showed that Vegfb was tightly co-expressed with nuclear-encoded mitochondrial genes across a large variety of physiological conditions in mice, pointing to a role for VEGF-B in metabolism. VEGF-B specifically controlled endothelial uptake of fatty acids via transcriptional regulation of vascular fatty acid transport proteins. As a consequence, Vegfb-/- mice showed less uptake and accumulation of lipids in muscle, heart and brown adipose tissue, and instead shunted lipids to white adipose tissue. This regulation was mediated by VEGF receptor 1 and neuropilin 1 expressed by the endothelium. The co-expression of VEGF-B and mitochondrial proteins introduces a novel regulatory mechanism, whereby endothelial lipid uptake and mitochondrial lipid use are tightly coordinated. The involvement of VEGF-B in lipid uptake may open up the possibility for novel strategies to modulate pathological lipid accumulation in diabetes, obesity and cardiovascular diseases.
Editor: London: Nature Publishing Group
Idioma: Inglês

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Vascular endothelial growth factor B controls endothelial fatty acid uptake

London: Nature Publishing Group

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