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Myeloid-Cell-Derived VEGF Maintains Brain Glucose Uptake and Limits Cognitive Impairment in Obesity
- Source :
- Cell, vol 165, iss 4
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
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(Δmyel) mice impairs BBB-GLUT1 expression, brain glucose uptake, and memory formation in obese, but not inlean 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-associatedmacrophage activation a homeostatic role torestore cerebral glucose metabolism, preserve cognitive function, and limit neurodegeneration in obesity.
- Subjects :
- Vascular Endothelial Growth Factor A
0301 basic medicine
Glucose uptake
Neurodegenerative
Cardiovascular
Medical and Health Sciences
Mice
chemistry.chemical_compound
Cognition
2.1 Biological and endogenous factors
Myeloid Cells
Aetiology
Cognitive decline
Glucose Transporter Type 1
Diabetes
Fatty Acids
Brain
Biological Sciences
Vascular endothelial growth factor
medicine.anatomical_structure
Blood-Brain Barrier
medicine.medical_specialty
1.1 Normal biological development and functioning
Biology
Diet, High-Fat
Blood–brain barrier
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
Underpinning research
Internal medicine
Acquired Cognitive Impairment
medicine
Animals
Obesity
Neuroinflammation
Nutrition
Neurosciences
Glucose transporter
Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD)
Endothelial Cells
nutritional and metabolic diseases
Brain Disorders
Diet
High-Fat
Glucose
030104 developmental biology
Endocrinology
chemistry
biology.protein
Dementia
GLUT1
Developmental Biology
Subjects
Details
- ISSN :
- 00928674
- Volume :
- 165
- Database :
- OpenAIRE
- Journal :
- Cell
- Accession number :
- edsair.doi.dedup.....c1529a404d795e816a3ab545a128ca55