title: Tanycytic VEGF-A boosts blood-hypothalamus barrier plasticity and access of metabolic signals to the arcuate nucleus in response to fasting.
abstract: The delivery of blood-borne molecules conveying metabolic information to neural networks that regulate energy homeostasis is restricted by brain barriers. The fenestrated endothelium of median eminence microvessels and tight junctions between tanycytes together compose one of these. Here, we show that the decrease in blood glucose levels during fasting alters the structural organization of this blood-hypothalamus barrier, resulting in the improved access of metabolic substrates to the arcuate nucleus. These changes are mimicked by 2-deoxyglucose-induced glucoprivation and reversed by raising blood glucose levels after fasting. Furthermore, we show that VEGF-A expression in tanycytes modulates these barrier properties. The neutralization of VEGF signaling blocks fasting-induced barrier remodeling and significantly impairs the physiological response to refeeding. These results implicate glucose in the control of blood-hypothalamus exchanges through a VEGF-dependent mechanism and demonstrate a hitherto unappreciated role for tanycytes and the permeable microvessels associated with them in the adaptive metabolic response to fasting.
authors.affiliation: Laboratory of Development and Plasticity of the Postnatal Brain, Jean-Pierre Aubert Research Centre, Inserm U837, 59000 Lille, France.
authors.forename: Fanny
authors.initials: F
authors.lastname: Langlet
authors.forename: Barry E
authors.initials: BE
authors.lastname: Levin
authors.forename: Serge
authors.initials: S
authors.lastname: Luquet
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Mazzone
authors.forename: Andrea
authors.initials: A
authors.lastname: Messina
authors.forename: Ambrose A
authors.initials: AA
authors.lastname: Dunn-Meynell
authors.forename: Eglantine
authors.initials: E
authors.lastname: Balland
authors.forename: Amelie
authors.initials: A
authors.lastname: Lacombe
authors.forename: Daniele
authors.initials: D
authors.lastname: Mazur
authors.forename: Peter
authors.initials: P
authors.lastname: Carmeliet
authors.forename: Sebastien G
authors.initials: SG
authors.lastname: Bouret
authors.forename: Vincent
authors.initials: V
authors.lastname: Prevot
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Dehouck
mesh_terms: D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism*; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism*; D003847:Deoxyglucose / Q000494:pharmacology; D004805:Ependyma / Q000166:cytology / Q000378:metabolism*; D005215:Fasting; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction; D019108:Tight Junctions / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
chemical_list: D042461:Vascular Endothelial Growth Factor A; D003847:Deoxyglucose
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