过剩1
内分泌学
内科学
生物
葡萄糖转运蛋白
葡萄糖摄取
神经炎症
血脑屏障
神经退行性变
血管生成
血管内皮生长因子
碳水化合物代谢
下调和上调
癌症研究
免疫学
胰岛素
中枢神经系统
医学
炎症
疾病
血管内皮生长因子受体
生物化学
基因
作者
Alexander Jais,Maite Solas,Heiko Backes,Bhagirath Chaurasia,André Kleinridders,Sebastian Theurich,Jan Mauer,Sophie M. Steculorum,Brigitte Hampel,Julia Goldau,Jens Alber,Carola Förster,Sabine A. Eming,Markus Schwaninger,Napoleone Ferrara,G. Karsenty,Jens C. Brüning
出处
期刊:Cell
[Elsevier]
日期:2016-05-01
卷期号:165 (4): 882-895
被引量:164
标识
DOI:10.1016/j.cell.2016.03.033
摘要
High-fat diet (HFD) feeding induces rapid reprogramming of systemic metabolism. Here, we demonstrate that HFD feeding of mice downregulates glucose transporter (GLUT)-1 expression in blood-brain barrier (BBB) vascular endothelial cells (BECs) and reduces brain glucose uptake. Upon prolonged HFD feeding, GLUT1 expression is restored, which is paralleled by increased expression of vascular endothelial growth factor (VEGF) in macrophages at the BBB. In turn, inducible reduction of GLUT1 expression specifically in BECs reduces brain glucose uptake and increases VEGF serum concentrations in lean mice. Conversely, myeloid-cell-specific deletion of VEGF in VEGF(Δmyel) mice impairs BBB-GLUT1 expression, brain glucose uptake, and memory formation in obese, but not in lean mice. Moreover, obese VEGF(Δmyel) mice exhibit exaggerated progression of cognitive decline and neuroinflammation on an Alzheimer's disease background. These experiments reveal that transient, HFD-elicited reduction of brain glucose uptake initiates a compensatory increase of VEGF production and assign obesity-associated macrophage activation a homeostatic role to restore cerebral glucose metabolism, preserve cognitive function, and limit neurodegeneration in obesity.
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