Cargando…
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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1784759824576151552 |
---|---|
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. |
format | Online Article Text |
id | pubmed-9337767 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT katashimacarloskiyoshi evidenceforaneuromuscularcircuitinvolvinghypothalamicinterleukin6inthecontrolofskeletalmusclemetabolism AT deoliveiramichelettithayana evidenceforaneuromuscularcircuitinvolvinghypothalamicinterleukin6inthecontrolofskeletalmusclemetabolism AT bragarenatarosseto evidenceforaneuromuscularcircuitinvolvinghypothalamicinterleukin6inthecontrolofskeletalmusclemetabolism AT gasparrodrigostellzer evidenceforaneuromuscularcircuitinvolvinghypothalamicinterleukin6inthecontrolofskeletalmusclemetabolism AT goeminneludgerje evidenceforaneuromuscularcircuitinvolvinghypothalamicinterleukin6inthecontrolofskeletalmusclemetabolism AT mouraassisalexandre evidenceforaneuromuscularcircuitinvolvinghypothalamicinterleukin6inthecontrolofskeletalmusclemetabolism AT crisolbarbaramoreira evidenceforaneuromuscularcircuitinvolvinghypothalamicinterleukin6inthecontrolofskeletalmusclemetabolism AT bricolarafaels evidenceforaneuromuscularcircuitinvolvinghypothalamicinterleukin6inthecontrolofskeletalmusclemetabolism AT silvavagnerramonr evidenceforaneuromuscularcircuitinvolvinghypothalamicinterleukin6inthecontrolofskeletalmusclemetabolism AT deoliveiraramoscamila evidenceforaneuromuscularcircuitinvolvinghypothalamicinterleukin6inthecontrolofskeletalmusclemetabolism AT darochaalissonl evidenceforaneuromuscularcircuitinvolvinghypothalamicinterleukin6inthecontrolofskeletalmusclemetabolism AT tavaresmarianarosolen evidenceforaneuromuscularcircuitinvolvinghypothalamicinterleukin6inthecontrolofskeletalmusclemetabolism AT simabucofernandomoreira evidenceforaneuromuscularcircuitinvolvinghypothalamicinterleukin6inthecontrolofskeletalmusclemetabolism AT matheusvalquiriaaparecida evidenceforaneuromuscularcircuitinvolvinghypothalamicinterleukin6inthecontrolofskeletalmusclemetabolism AT buscarattilucas evidenceforaneuromuscularcircuitinvolvinghypothalamicinterleukin6inthecontrolofskeletalmusclemetabolism AT marquessouzahenrique evidenceforaneuromuscularcircuitinvolvinghypothalamicinterleukin6inthecontrolofskeletalmusclemetabolism AT pazospatricia evidenceforaneuromuscularcircuitinvolvinghypothalamicinterleukin6inthecontrolofskeletalmusclemetabolism AT gonzaleztoucedadavid evidenceforaneuromuscularcircuitinvolvinghypothalamicinterleukin6inthecontrolofskeletalmusclemetabolism AT tovarsulay evidenceforaneuromuscularcircuitinvolvinghypothalamicinterleukin6inthecontrolofskeletalmusclemetabolism AT delcarmengarciamaria evidenceforaneuromuscularcircuitinvolvinghypothalamicinterleukin6inthecontrolofskeletalmusclemetabolism AT netojosecesarrosa evidenceforaneuromuscularcircuitinvolvinghypothalamicinterleukin6inthecontrolofskeletalmusclemetabolism AT curirui evidenceforaneuromuscularcircuitinvolvinghypothalamicinterleukin6inthecontrolofskeletalmusclemetabolism AT hirabarasandromassao evidenceforaneuromuscularcircuitinvolvinghypothalamicinterleukin6inthecontrolofskeletalmusclemetabolism AT brumpatriciachakur evidenceforaneuromuscularcircuitinvolvinghypothalamicinterleukin6inthecontrolofskeletalmusclemetabolism AT pradapatriciaoliveira evidenceforaneuromuscularcircuitinvolvinghypothalamicinterleukin6inthecontrolofskeletalmusclemetabolism AT demouraleandrop evidenceforaneuromuscularcircuitinvolvinghypothalamicinterleukin6inthecontrolofskeletalmusclemetabolism AT paulijoserodrigo evidenceforaneuromuscularcircuitinvolvinghypothalamicinterleukin6inthecontrolofskeletalmusclemetabolism AT dasilvaadelinosr evidenceforaneuromuscularcircuitinvolvinghypothalamicinterleukin6inthecontrolofskeletalmusclemetabolism AT cintradennysesper evidenceforaneuromuscularcircuitinvolvinghypothalamicinterleukin6inthecontrolofskeletalmusclemetabolism AT vellosolicioa evidenceforaneuromuscularcircuitinvolvinghypothalamicinterleukin6inthecontrolofskeletalmusclemetabolism AT ropelleeduardorochete evidenceforaneuromuscularcircuitinvolvinghypothalamicinterleukin6inthecontrolofskeletalmusclemetabolism |