EphrinB1 modulates glutamatergic inputs into POMC-expressing progenitors and controls glucose homeostasis.

Details

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State: Public
Version: author
License: CC BY 4.0
Serval ID
serval:BIB_342F83D79CC2
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
EphrinB1 modulates glutamatergic inputs into POMC-expressing progenitors and controls glucose homeostasis.
Journal
PLoS biology
Author(s)
Gervais M., Labouèbe G., Picard A., Thorens B., Croizier S.
ISSN
1545-7885 (Electronic)
ISSN-L
1544-9173
Publication state
Published
Issued date
11/2020
Peer-reviewed
Oui
Volume
18
Number
11
Pages
e3000680
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
Proopiomelanocortin (POMC) neurons are major regulators of energy balance and glucose homeostasis. In addition to being regulated by hormones and nutrients, POMC neurons are controlled by glutamatergic input originating from multiple brain regions. However, the factors involved in the formation of glutamatergic inputs and how they contribute to bodily functions remain largely unknown. Here, we show that during the development of glutamatergic inputs, POMC neurons exhibit enriched expression of the Efnb1 (EphrinB1) and Efnb2 (EphrinB2) genes, which are known to control excitatory synapse formation. In vivo loss of Efnb1 in POMC-expressing progenitors decreases the amount of glutamatergic inputs, associated with a reduced number of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptor subunits and excitability of these cells. We found that mice lacking Efnb1 in POMC-expressing progenitors display impaired glucose tolerance due to blunted vagus nerve activity and decreased insulin secretion. However, despite reduced excitatory inputs, mice lacking Efnb2 in POMC-expressing progenitors showed no deregulation of insulin secretion and only mild alterations in feeding behavior and gluconeogenesis. Collectively, our data demonstrate the role of ephrins in controlling excitatory input amount into POMC-expressing progenitors and show an isotype-specific role of ephrins on the regulation of glucose homeostasis and feeding.
Keywords
Animals, Brain/metabolism, Energy Metabolism/physiology, Ephrin-B1/metabolism, Ephrin-B1/physiology, Ephrin-B2/metabolism, Ephrin-B2/physiology, Excitatory Amino Acid Agents/metabolism, Glucose/metabolism, Homeostasis/physiology, Male, Mice, Mice, Knockout, N-Methylaspartate/metabolism, Neurons/metabolism, Pro-Opiomelanocortin/metabolism, Receptors, N-Methyl-D-Aspartate/metabolism, alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
07/12/2020 14:52
Last modification date
09/12/2023 7:02
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