Journal article
Myeloid-Cell-Derived VEGF Maintains Brain Glucose Uptake and Limits Cognitive Impairment in Obesity
Cell, Vol.165(4), pp.882-895
05/05/2016
DOI: 10.1016/j.cell.2016.03.033
PMID: 27133169
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.
Details
- Title: Subtitle
- Myeloid-Cell-Derived VEGF Maintains Brain Glucose Uptake and Limits Cognitive Impairment in Obesity
- Creators
- Alexander Jais - Max Planck Institute for Metabolism ResearchMaite Solas - Max Planck Institute for Metabolism ResearchHeiko Backes - Max Planck Institute for Metabolism ResearchBhagirath Chaurasia - Max Planck Institute for Metabolism ResearchAndre Kleinridders - Max Planck Institute for Metabolism ResearchSebastian Theurich - Max Planck Institute for Metabolism ResearchJan Mauer - Max Planck Institute for Metabolism ResearchSophie M. Steculorum - Max Planck Institute for Metabolism ResearchBrigitte Hampel - Max Planck Institute for Metabolism ResearchJulia Goldau - Max Planck Institute for Metabolism ResearchJens Alber - Max Planck Institute for Metabolism ResearchCarola Y. Foerster - University of WürzburgSabine A. Eming - Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated DiseasesMarkus Schwaninger - Med Univ Lubeck, Inst Expt & Clin Pharmacol & Toxicol, Ratzeburger Allee 160, D-23562 Lubeck, GermanyNapoleone Ferrara - University of California, San DiegoGerard Karsenty - Columbia UniversityJens C. Bruening - Max Planck Institute for Metabolism Research
- Resource Type
- Journal article
- Publication Details
- Cell, Vol.165(4), pp.882-895
- Publisher
- Elsevier
- DOI
- 10.1016/j.cell.2016.03.033
- PMID
- 27133169
- ISSN
- 0092-8674
- eISSN
- 1097-4172
- Number of pages
- 14
- Grant note
- Humboldt-Bayer program of the Alexander Von Humboldt foundation; Alexander von Humboldt Foundation 1R01DK104727-01A1 / National Institute on Aging (NIA); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA) CMMC Excellence Initiative by German State Government R01DK104727 / NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) BR 1492/7-1; TRR134; KL2399-3/1 / DFG; German Research Foundation (DFG) Helmholtz Alliance ICEMED (Imaging and Curing Environmental Metabolic Diseases) through the Initiative and Networking Fund of the Helmholtz Association 266408 / European Union; European Commission Excellence Initiative by German Federal Government Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD) 3/2014 / Medical Faculty of the University of Cologne
- Language
- English
- Date published
- 05/05/2016
- Academic Unit
- Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984359843202771
Metrics
6 Record Views