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Blockade of Glial Connexin 43 Hemichannels Reduces Food Intake

The metabolic syndrome, which comprises obesity and diabetes, is a major public health problem and the awareness of energy homeostasis control remains an important worldwide issue. The energy balance is finely regulated by the central nervous system (CNS), notably through neuronal networks, located...

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Autores principales: Guillebaud, Florent, Barbot, Manon, Barbouche, Rym, Brézun, Jean-Michel, Poirot, Kevin, Vasile, Flora, Lebrun, Bruno, Rouach, Nathalie, Dallaporta, Michel, Gaige, Stéphanie, Troadec, Jean-Denis
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693394/
https://www.ncbi.nlm.nih.gov/pubmed/33142723
http://dx.doi.org/10.3390/cells9112387
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author Guillebaud, Florent
Barbot, Manon
Barbouche, Rym
Brézun, Jean-Michel
Poirot, Kevin
Vasile, Flora
Lebrun, Bruno
Rouach, Nathalie
Dallaporta, Michel
Gaige, Stéphanie
Troadec, Jean-Denis
author_facet Guillebaud, Florent
Barbot, Manon
Barbouche, Rym
Brézun, Jean-Michel
Poirot, Kevin
Vasile, Flora
Lebrun, Bruno
Rouach, Nathalie
Dallaporta, Michel
Gaige, Stéphanie
Troadec, Jean-Denis
author_sort Guillebaud, Florent
collection PubMed
description The metabolic syndrome, which comprises obesity and diabetes, is a major public health problem and the awareness of energy homeostasis control remains an important worldwide issue. The energy balance is finely regulated by the central nervous system (CNS), notably through neuronal networks, located in the hypothalamus and the dorsal vagal complex (DVC), which integrate nutritional, humoral and nervous information from the periphery. The glial cells’ contribution to these processes emerged few year ago. However, its underlying mechanism remains unclear. Glial connexin 43 hemichannels (Cx43 HCs) enable direct exchange with the extracellular space and can regulate neuronal network activity. In the present study, we sought to determine the possible involvement of glial Cx43 HCs in energy balance regulation. We here show that Cx43 is strongly expressed in the hypothalamus and DVC and is associated with glial cells. Remarkably, we observed a close apposition of Cx43 with synaptic elements in both the hypothalamus and DVC. Moreover, the expression of hypothalamic Cx43 mRNA and protein is modulated in response to fasting and diet-induced obesity. Functionally, we found that Cx43 HCs are largely open in the arcuate nucleus (ARC) from acute mice hypothalamic slices under basal condition, and significantly inhibited by TAT-GAP19, a mimetic peptide that specifically blocks Cx43 HCs activity. Moreover, intracerebroventricular (i.c.v.) TAT-GAP19 injection strongly decreased food intake, without further alteration of glycaemia, energy expenditures or locomotor activity. Using the immediate early gene c-Fos expression, we found that i.c.v. TAT-GAP19 injection induced neuronal activation in hypothalamic and brainstem nuclei dedicated to food intake regulation. Altogether, these results suggest a tonic delivery of orexigenic molecules associated with glial Cx43 HCs activity and a possible modulation of this tonus during fasting and obesity.
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spelling pubmed-76933942020-11-28 Blockade of Glial Connexin 43 Hemichannels Reduces Food Intake Guillebaud, Florent Barbot, Manon Barbouche, Rym Brézun, Jean-Michel Poirot, Kevin Vasile, Flora Lebrun, Bruno Rouach, Nathalie Dallaporta, Michel Gaige, Stéphanie Troadec, Jean-Denis Cells Article The metabolic syndrome, which comprises obesity and diabetes, is a major public health problem and the awareness of energy homeostasis control remains an important worldwide issue. The energy balance is finely regulated by the central nervous system (CNS), notably through neuronal networks, located in the hypothalamus and the dorsal vagal complex (DVC), which integrate nutritional, humoral and nervous information from the periphery. The glial cells’ contribution to these processes emerged few year ago. However, its underlying mechanism remains unclear. Glial connexin 43 hemichannels (Cx43 HCs) enable direct exchange with the extracellular space and can regulate neuronal network activity. In the present study, we sought to determine the possible involvement of glial Cx43 HCs in energy balance regulation. We here show that Cx43 is strongly expressed in the hypothalamus and DVC and is associated with glial cells. Remarkably, we observed a close apposition of Cx43 with synaptic elements in both the hypothalamus and DVC. Moreover, the expression of hypothalamic Cx43 mRNA and protein is modulated in response to fasting and diet-induced obesity. Functionally, we found that Cx43 HCs are largely open in the arcuate nucleus (ARC) from acute mice hypothalamic slices under basal condition, and significantly inhibited by TAT-GAP19, a mimetic peptide that specifically blocks Cx43 HCs activity. Moreover, intracerebroventricular (i.c.v.) TAT-GAP19 injection strongly decreased food intake, without further alteration of glycaemia, energy expenditures or locomotor activity. Using the immediate early gene c-Fos expression, we found that i.c.v. TAT-GAP19 injection induced neuronal activation in hypothalamic and brainstem nuclei dedicated to food intake regulation. Altogether, these results suggest a tonic delivery of orexigenic molecules associated with glial Cx43 HCs activity and a possible modulation of this tonus during fasting and obesity. MDPI 2020-10-31 /pmc/articles/PMC7693394/ /pubmed/33142723 http://dx.doi.org/10.3390/cells9112387 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Guillebaud, Florent
Barbot, Manon
Barbouche, Rym
Brézun, Jean-Michel
Poirot, Kevin
Vasile, Flora
Lebrun, Bruno
Rouach, Nathalie
Dallaporta, Michel
Gaige, Stéphanie
Troadec, Jean-Denis
Blockade of Glial Connexin 43 Hemichannels Reduces Food Intake
title Blockade of Glial Connexin 43 Hemichannels Reduces Food Intake
title_full Blockade of Glial Connexin 43 Hemichannels Reduces Food Intake
title_fullStr Blockade of Glial Connexin 43 Hemichannels Reduces Food Intake
title_full_unstemmed Blockade of Glial Connexin 43 Hemichannels Reduces Food Intake
title_short Blockade of Glial Connexin 43 Hemichannels Reduces Food Intake
title_sort blockade of glial connexin 43 hemichannels reduces food intake
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693394/
https://www.ncbi.nlm.nih.gov/pubmed/33142723
http://dx.doi.org/10.3390/cells9112387
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