Universität zu Köln

Jais, Alexander ORCID: 0000-0002-9897-4983, Solas, Maite ORCID: 0000-0001-7670-3237, Backes, Heiko, Chaurasia, Bhagirath, Kleinridders, Andre ORCID: 0000-0002-4248-6366, Theurich, Sebastian ORCID: 0000-0001-5706-8258, Mauer, Jan ORCID: 0000-0002-0189-5876, Steculorum, Sophie M., Hampel, Brigitte, Goldau, Julia, Alber, Jens, Foerster, Carola Y., Eming, Sabine A., Schwaninger, Markus ORCID: 0000-0002-4510-9718, Ferrara, Napoleone, Karsenty, Gerard ORCID: 0000-0002-9253-7627 and Bruening, Jens C. (2016). Myeloid-Cell-Derived VEGF Maintains Brain Glucose Uptake and Limits Cognitive Impairment in Obesity. Cell, 165 (4). S. 882 - 896. CAMBRIDGE: CELL PRESS. ISSN 1097-4172

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Abstract

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 Dmyel mice impairs BBB-GLUT1 expression, brain glucose uptake, and memory formation in obese, but not in lean mice. Moreover, obese VEGF Dmyel 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Jais, Alexander UNSPECIFIED orcid.org/0000-0002-9897-4983 UNSPECIFIED Solas, Maite UNSPECIFIED orcid.org/0000-0001-7670-3237 UNSPECIFIED Backes, Heiko UNSPECIFIED UNSPECIFIED UNSPECIFIED Chaurasia, Bhagirath UNSPECIFIED UNSPECIFIED UNSPECIFIED Kleinridders, Andre UNSPECIFIED orcid.org/0000-0002-4248-6366 UNSPECIFIED Theurich, Sebastian UNSPECIFIED orcid.org/0000-0001-5706-8258 UNSPECIFIED Mauer, Jan UNSPECIFIED orcid.org/0000-0002-0189-5876 UNSPECIFIED Steculorum, Sophie M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hampel, Brigitte UNSPECIFIED UNSPECIFIED UNSPECIFIED Goldau, Julia UNSPECIFIED UNSPECIFIED UNSPECIFIED Alber, Jens UNSPECIFIED UNSPECIFIED UNSPECIFIED Foerster, Carola Y. UNSPECIFIED UNSPECIFIED UNSPECIFIED Eming, Sabine A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schwaninger, Markus UNSPECIFIED orcid.org/0000-0002-4510-9718 UNSPECIFIED Ferrara, Napoleone UNSPECIFIED UNSPECIFIED UNSPECIFIED Karsenty, Gerard UNSPECIFIED orcid.org/0000-0002-9253-7627 UNSPECIFIED Bruening, Jens C. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-275892
DOI:	10.1016/j.cell.2016.03.033
Journal or Publication Title:	Cell
Volume:	165
Number:	4
Page Range:	S. 882 - 896
Date:	2016
Publisher:	CELL PRESS
Place of Publication:	CAMBRIDGE
ISSN:	1097-4172
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language INDUCED INSULIN-RESISTANCE; ENDOTHELIAL GROWTH-FACTOR; ENERGY HOMEOSTASIS; ALZHEIMERS-DISEASE; IMMUNE-SYSTEM; IN-VIVO; MACROPHAGES; TRANSPORTER; BARRIER; CNS Multiple languages Biochemistry & Molecular Biology; Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/27589