Cargando…
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...
Autores principales: | , , , , , , , , , , |
---|---|
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 |
_version_ | 1783614734040301568 |
---|---|
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. |
format | Online Article Text |
id | pubmed-7693394 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT guillebaudflorent blockadeofglialconnexin43hemichannelsreducesfoodintake AT barbotmanon blockadeofglialconnexin43hemichannelsreducesfoodintake AT barboucherym blockadeofglialconnexin43hemichannelsreducesfoodintake AT brezunjeanmichel blockadeofglialconnexin43hemichannelsreducesfoodintake AT poirotkevin blockadeofglialconnexin43hemichannelsreducesfoodintake AT vasileflora blockadeofglialconnexin43hemichannelsreducesfoodintake AT lebrunbruno blockadeofglialconnexin43hemichannelsreducesfoodintake AT rouachnathalie blockadeofglialconnexin43hemichannelsreducesfoodintake AT dallaportamichel blockadeofglialconnexin43hemichannelsreducesfoodintake AT gaigestephanie blockadeofglialconnexin43hemichannelsreducesfoodintake AT troadecjeandenis blockadeofglialconnexin43hemichannelsreducesfoodintake |