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.

journal_name

Cell Metab

journal_title

Cell metabolism

authors

Langlet F,Levin BE,Luquet S,Mazzone M,Messina A,Dunn-Meynell AA,Balland E,Lacombe A,Mazur D,Carmeliet P,Bouret SG,Prevot V,Dehouck B

doi

10.1016/j.cmet.2013.03.004

subject

Has Abstract

pub_date

2013-04-02 00:00:00

pages

607-17

issue

4

eissn

1550-4131

issn

1932-7420

pii

S1550-4131(13)00107-1

journal_volume

17

pub_type

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