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Evidence for a neuromuscular circuit involving hypothalamic interleukin-6 in the control of skeletal muscle metabolism

Hypothalamic interleukin-6 (IL6) exerts a broad metabolic control. Here, we demonstrated that IL6 activates the ERK1/2 pathway in the ventromedial hypothalamus (VMH), stimulating AMPK/ACC signaling and fatty acid oxidation in mouse skeletal muscle. Bioinformatics analysis revealed that the hypothala...

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Autores principales: Katashima, Carlos Kiyoshi, de Oliveira Micheletti, Thayana, Braga, Renata Rosseto, Gaspar, Rodrigo Stellzer, Goeminne, Ludger J. E., Moura-Assis, Alexandre, Crisol, Barbara Moreira, Brícola, Rafael S., Silva, Vagner Ramon R., de Oliveira Ramos, Camila, da Rocha, Alisson L., Tavares, Mariana Rosolen, Simabuco, Fernando Moreira, Matheus, Valquiria Aparecida, Buscaratti, Lucas, Marques-Souza, Henrique, Pazos, Patricia, Gonzalez-Touceda, David, Tovar, Sulay, del Carmen García, María, Neto, Jose Cesar Rosa, Curi, Rui, Hirabara, Sandro Massao, Brum, Patrícia Chakur, Prada, Patrícia Oliveira, de Moura, Leandro P., Pauli, José Rodrigo, da Silva, Adelino S. R., Cintra, Dennys Esper, Velloso, Licio A., Ropelle, Eduardo Rochete
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9337767/
https://www.ncbi.nlm.nih.gov/pubmed/35905178
http://dx.doi.org/10.1126/sciadv.abm7355
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author Katashima, Carlos Kiyoshi
de Oliveira Micheletti, Thayana
Braga, Renata Rosseto
Gaspar, Rodrigo Stellzer
Goeminne, Ludger J. E.
Moura-Assis, Alexandre
Crisol, Barbara Moreira
Brícola, Rafael S.
Silva, Vagner Ramon R.
de Oliveira Ramos, Camila
da Rocha, Alisson L.
Tavares, Mariana Rosolen
Simabuco, Fernando Moreira
Matheus, Valquiria Aparecida
Buscaratti, Lucas
Marques-Souza, Henrique
Pazos, Patricia
Gonzalez-Touceda, David
Tovar, Sulay
del Carmen García, María
Neto, Jose Cesar Rosa
Curi, Rui
Hirabara, Sandro Massao
Brum, Patrícia Chakur
Prada, Patrícia Oliveira
de Moura, Leandro P.
Pauli, José Rodrigo
da Silva, Adelino S. R.
Cintra, Dennys Esper
Velloso, Licio A.
Ropelle, Eduardo Rochete
author_facet Katashima, Carlos Kiyoshi
de Oliveira Micheletti, Thayana
Braga, Renata Rosseto
Gaspar, Rodrigo Stellzer
Goeminne, Ludger J. E.
Moura-Assis, Alexandre
Crisol, Barbara Moreira
Brícola, Rafael S.
Silva, Vagner Ramon R.
de Oliveira Ramos, Camila
da Rocha, Alisson L.
Tavares, Mariana Rosolen
Simabuco, Fernando Moreira
Matheus, Valquiria Aparecida
Buscaratti, Lucas
Marques-Souza, Henrique
Pazos, Patricia
Gonzalez-Touceda, David
Tovar, Sulay
del Carmen García, María
Neto, Jose Cesar Rosa
Curi, Rui
Hirabara, Sandro Massao
Brum, Patrícia Chakur
Prada, Patrícia Oliveira
de Moura, Leandro P.
Pauli, José Rodrigo
da Silva, Adelino S. R.
Cintra, Dennys Esper
Velloso, Licio A.
Ropelle, Eduardo Rochete
author_sort Katashima, Carlos Kiyoshi
collection PubMed
description Hypothalamic interleukin-6 (IL6) exerts a broad metabolic control. Here, we demonstrated that IL6 activates the ERK1/2 pathway in the ventromedial hypothalamus (VMH), stimulating AMPK/ACC signaling and fatty acid oxidation in mouse skeletal muscle. Bioinformatics analysis revealed that the hypothalamic IL6/ERK1/2 axis is closely associated with fatty acid oxidation– and mitochondrial-related genes in the skeletal muscle of isogenic BXD mouse strains and humans. We showed that the hypothalamic IL6/ERK1/2 pathway requires the α2-adrenergic pathway to modify fatty acid skeletal muscle metabolism. To address the physiological relevance of these findings, we demonstrated that this neuromuscular circuit is required to underpin AMPK/ACC signaling activation and fatty acid oxidation after exercise. Last, the selective down-regulation of IL6 receptor in VMH abolished the effects of exercise to sustain AMPK and ACC phosphorylation and fatty acid oxidation in the muscle after exercise. Together, these data demonstrated that the IL6/ERK axis in VMH controls fatty acid metabolism in the skeletal muscle.
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spelling pubmed-93377672022-08-09 Evidence for a neuromuscular circuit involving hypothalamic interleukin-6 in the control of skeletal muscle metabolism Katashima, Carlos Kiyoshi de Oliveira Micheletti, Thayana Braga, Renata Rosseto Gaspar, Rodrigo Stellzer Goeminne, Ludger J. E. Moura-Assis, Alexandre Crisol, Barbara Moreira Brícola, Rafael S. Silva, Vagner Ramon R. de Oliveira Ramos, Camila da Rocha, Alisson L. Tavares, Mariana Rosolen Simabuco, Fernando Moreira Matheus, Valquiria Aparecida Buscaratti, Lucas Marques-Souza, Henrique Pazos, Patricia Gonzalez-Touceda, David Tovar, Sulay del Carmen García, María Neto, Jose Cesar Rosa Curi, Rui Hirabara, Sandro Massao Brum, Patrícia Chakur Prada, Patrícia Oliveira de Moura, Leandro P. Pauli, José Rodrigo da Silva, Adelino S. R. Cintra, Dennys Esper Velloso, Licio A. Ropelle, Eduardo Rochete Sci Adv Biomedicine and Life Sciences Hypothalamic interleukin-6 (IL6) exerts a broad metabolic control. Here, we demonstrated that IL6 activates the ERK1/2 pathway in the ventromedial hypothalamus (VMH), stimulating AMPK/ACC signaling and fatty acid oxidation in mouse skeletal muscle. Bioinformatics analysis revealed that the hypothalamic IL6/ERK1/2 axis is closely associated with fatty acid oxidation– and mitochondrial-related genes in the skeletal muscle of isogenic BXD mouse strains and humans. We showed that the hypothalamic IL6/ERK1/2 pathway requires the α2-adrenergic pathway to modify fatty acid skeletal muscle metabolism. To address the physiological relevance of these findings, we demonstrated that this neuromuscular circuit is required to underpin AMPK/ACC signaling activation and fatty acid oxidation after exercise. Last, the selective down-regulation of IL6 receptor in VMH abolished the effects of exercise to sustain AMPK and ACC phosphorylation and fatty acid oxidation in the muscle after exercise. Together, these data demonstrated that the IL6/ERK axis in VMH controls fatty acid metabolism in the skeletal muscle. American Association for the Advancement of Science 2022-07-29 /pmc/articles/PMC9337767/ /pubmed/35905178 http://dx.doi.org/10.1126/sciadv.abm7355 Text en Copyright © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.
spellingShingle Biomedicine and Life Sciences
Katashima, Carlos Kiyoshi
de Oliveira Micheletti, Thayana
Braga, Renata Rosseto
Gaspar, Rodrigo Stellzer
Goeminne, Ludger J. E.
Moura-Assis, Alexandre
Crisol, Barbara Moreira
Brícola, Rafael S.
Silva, Vagner Ramon R.
de Oliveira Ramos, Camila
da Rocha, Alisson L.
Tavares, Mariana Rosolen
Simabuco, Fernando Moreira
Matheus, Valquiria Aparecida
Buscaratti, Lucas
Marques-Souza, Henrique
Pazos, Patricia
Gonzalez-Touceda, David
Tovar, Sulay
del Carmen García, María
Neto, Jose Cesar Rosa
Curi, Rui
Hirabara, Sandro Massao
Brum, Patrícia Chakur
Prada, Patrícia Oliveira
de Moura, Leandro P.
Pauli, José Rodrigo
da Silva, Adelino S. R.
Cintra, Dennys Esper
Velloso, Licio A.
Ropelle, Eduardo Rochete
Evidence for a neuromuscular circuit involving hypothalamic interleukin-6 in the control of skeletal muscle metabolism
title Evidence for a neuromuscular circuit involving hypothalamic interleukin-6 in the control of skeletal muscle metabolism
title_full Evidence for a neuromuscular circuit involving hypothalamic interleukin-6 in the control of skeletal muscle metabolism
title_fullStr Evidence for a neuromuscular circuit involving hypothalamic interleukin-6 in the control of skeletal muscle metabolism
title_full_unstemmed Evidence for a neuromuscular circuit involving hypothalamic interleukin-6 in the control of skeletal muscle metabolism
title_short Evidence for a neuromuscular circuit involving hypothalamic interleukin-6 in the control of skeletal muscle metabolism
title_sort evidence for a neuromuscular circuit involving hypothalamic interleukin-6 in the control of skeletal muscle metabolism
topic Biomedicine and Life Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9337767/
https://www.ncbi.nlm.nih.gov/pubmed/35905178
http://dx.doi.org/10.1126/sciadv.abm7355
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