Tanycytic VEGF-A boosts blood-hypothalamus barrier plasticity and access of metabolic signals to the arcuate nucleus in response to fasting

Fanny Langlet, Barry E Levin, Serge Luquet, Massimiliano Mazzone, Andrea Messina, Ambrose A Dunn-Meynell, Eglantine Balland, Amelie Lacombe, Daniele Mazur, Peter Carmeliet, Sebastien G Bouret, Vincent Prevot, Benedicte Dehouck

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169 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)607 - 617
Number of pages11
JournalCell Metabolism
Volume17
Issue number4
DOIs
Publication statusPublished - 2013
Externally publishedYes

Cite this

Langlet, F., Levin, B. E., Luquet, S., Mazzone, M., Messina, A., Dunn-Meynell, A. A., Balland, E., Lacombe, A., Mazur, D., Carmeliet, P., Bouret, S. G., Prevot, V., & Dehouck, B. (2013). Tanycytic VEGF-A boosts blood-hypothalamus barrier plasticity and access of metabolic signals to the arcuate nucleus in response to fasting. Cell Metabolism, 17(4), 607 - 617. https://doi.org/10.1016/j.cmet.2013.03.004