Vascular endothelial growth factor B controls endothelial fatty acid uptake
Vascular endothelial growth factor B controls endothelial fatty acid uptake
复制标题
DOI：
10.1038/nature08945
复制
发表时间：
2010-04-08
期刊：
影响因子：
64.8
通讯作者：
Eriksson, Ulf
中科院分区：
文献类型：
--
作者：
Hagberg, Carolina E.;Falkevall, Annelie;Eriksson, Ulf
血管内皮生长因子（VEGFs）是主要的血管生成调节因子，参与内皮细胞生理学的多个方面。然而，VEGF - B在血管功能中的具体作用仍不清楚。在此我们表明，VEGF - B在内皮将脂质靶向运输到外周组织方面具有意想不到的作用。循环中存在的膳食脂质必须通过血管内皮运输才能被组织细胞代谢，这一机制目前了解甚少。生物信息学分析显示，在小鼠的多种生理条件下，Vegfb与核编码的线粒体基因紧密共表达，这表明VEGF - B在代谢中起作用。VEGF - B通过对血管脂肪酸转运蛋白的转录调控，特异性地控制内皮对脂肪酸的摄取。因此，Vegfb（-/-）小鼠在肌肉、心脏和棕色脂肪组织中脂质的摄取和积累较少，而是将脂质转运到白色脂肪组织。这种调节是由内皮表达的VEGF受体1和神经纤毛蛋白1介导的。VEGF - B和线粒体蛋白的共表达引入了一种新的调节机制，即内皮脂质摄取和线粒体脂质利用紧密协调。VEGF - B参与脂质摄取可能为调节糖尿病、肥胖和心血管疾病中病理性脂质积累的新策略提供了可能性。
The vascular endothelial growth factors (VEGFs) are major angiogenic regulators and are involved in several aspects of endothelial cell physiology(1). However, the detailed role of VEGF-B in blood vessel function has remained unclear(2,3). 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(4). 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.