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IL-6 and IL-10 Anti-Inflammatory Activity Links Exercise to Hypothalamic Insulin and Leptin Sensitivity through IKKβ and ER Stress Inhibition
Overnutrition caused by overeating is associated with insulin and leptin resistance through IKKβ activation and endoplasmic reticulum (ER) stress in the hypothalamus. Here we show that physical exercise suppresses hyperphagia and associated hypothalamic IKKβ/NF-κB activation by a mechanism dependent...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2927536/ https://www.ncbi.nlm.nih.gov/pubmed/20808781 http://dx.doi.org/10.1371/journal.pbio.1000465 |
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author | Ropelle, Eduardo R. Flores, Marcelo B. Cintra, Dennys E. Rocha, Guilherme Z. Pauli, José R. Morari, Joseane de Souza, Claudio T. Moraes, Juliana C. Prada, Patrícia O. Guadagnini, Dioze Marin, Rodrigo M. Oliveira, Alexandre G. Augusto, Taize M. Carvalho, Hernandes F. Velloso, Lício A. Saad, Mario J. A. Carvalheira, José B. C. |
author_facet | Ropelle, Eduardo R. Flores, Marcelo B. Cintra, Dennys E. Rocha, Guilherme Z. Pauli, José R. Morari, Joseane de Souza, Claudio T. Moraes, Juliana C. Prada, Patrícia O. Guadagnini, Dioze Marin, Rodrigo M. Oliveira, Alexandre G. Augusto, Taize M. Carvalho, Hernandes F. Velloso, Lício A. Saad, Mario J. A. Carvalheira, José B. C. |
author_sort | Ropelle, Eduardo R. |
collection | PubMed |
description | Overnutrition caused by overeating is associated with insulin and leptin resistance through IKKβ activation and endoplasmic reticulum (ER) stress in the hypothalamus. Here we show that physical exercise suppresses hyperphagia and associated hypothalamic IKKβ/NF-κB activation by a mechanism dependent upon the pro-inflammatory cytokine interleukin (IL)-6. The disruption of hypothalamic-specific IL-6 action blocked the beneficial effects of exercise on the re-balance of food intake and insulin and leptin resistance. This molecular mechanism, mediated by physical activity, involves the anti-inflammatory protein IL-10, a core inhibitor of IKKβ/NF-κB signaling and ER stress. We report that exercise and recombinant IL-6 requires IL-10 expression to suppress hyperphagia-related obesity. Moreover, in contrast to control mice, exercise failed to reverse the pharmacological activation of IKKβ and ER stress in C3H/HeJ mice deficient in hypothalamic IL-6 and IL-10 signaling. Hence, inflammatory signaling in the hypothalamus links beneficial physiological effects of exercise to the central action of insulin and leptin. |
format | Text |
id | pubmed-2927536 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-29275362010-08-31 IL-6 and IL-10 Anti-Inflammatory Activity Links Exercise to Hypothalamic Insulin and Leptin Sensitivity through IKKβ and ER Stress Inhibition Ropelle, Eduardo R. Flores, Marcelo B. Cintra, Dennys E. Rocha, Guilherme Z. Pauli, José R. Morari, Joseane de Souza, Claudio T. Moraes, Juliana C. Prada, Patrícia O. Guadagnini, Dioze Marin, Rodrigo M. Oliveira, Alexandre G. Augusto, Taize M. Carvalho, Hernandes F. Velloso, Lício A. Saad, Mario J. A. Carvalheira, José B. C. PLoS Biol Research Article Overnutrition caused by overeating is associated with insulin and leptin resistance through IKKβ activation and endoplasmic reticulum (ER) stress in the hypothalamus. Here we show that physical exercise suppresses hyperphagia and associated hypothalamic IKKβ/NF-κB activation by a mechanism dependent upon the pro-inflammatory cytokine interleukin (IL)-6. The disruption of hypothalamic-specific IL-6 action blocked the beneficial effects of exercise on the re-balance of food intake and insulin and leptin resistance. This molecular mechanism, mediated by physical activity, involves the anti-inflammatory protein IL-10, a core inhibitor of IKKβ/NF-κB signaling and ER stress. We report that exercise and recombinant IL-6 requires IL-10 expression to suppress hyperphagia-related obesity. Moreover, in contrast to control mice, exercise failed to reverse the pharmacological activation of IKKβ and ER stress in C3H/HeJ mice deficient in hypothalamic IL-6 and IL-10 signaling. Hence, inflammatory signaling in the hypothalamus links beneficial physiological effects of exercise to the central action of insulin and leptin. Public Library of Science 2010-08-24 /pmc/articles/PMC2927536/ /pubmed/20808781 http://dx.doi.org/10.1371/journal.pbio.1000465 Text en © 2010 Ropelle et al https://creativecommons.org/licenses/by/4.0/Except for the Figure 2F IB: pJak2Tyr1007/8 panel. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Ropelle, Eduardo R. Flores, Marcelo B. Cintra, Dennys E. Rocha, Guilherme Z. Pauli, José R. Morari, Joseane de Souza, Claudio T. Moraes, Juliana C. Prada, Patrícia O. Guadagnini, Dioze Marin, Rodrigo M. Oliveira, Alexandre G. Augusto, Taize M. Carvalho, Hernandes F. Velloso, Lício A. Saad, Mario J. A. Carvalheira, José B. C. IL-6 and IL-10 Anti-Inflammatory Activity Links Exercise to Hypothalamic Insulin and Leptin Sensitivity through IKKβ and ER Stress Inhibition |
title | IL-6 and IL-10 Anti-Inflammatory Activity Links Exercise to Hypothalamic Insulin and Leptin Sensitivity through IKKβ and ER Stress Inhibition |
title_full | IL-6 and IL-10 Anti-Inflammatory Activity Links Exercise to Hypothalamic Insulin and Leptin Sensitivity through IKKβ and ER Stress Inhibition |
title_fullStr | IL-6 and IL-10 Anti-Inflammatory Activity Links Exercise to Hypothalamic Insulin and Leptin Sensitivity through IKKβ and ER Stress Inhibition |
title_full_unstemmed | IL-6 and IL-10 Anti-Inflammatory Activity Links Exercise to Hypothalamic Insulin and Leptin Sensitivity through IKKβ and ER Stress Inhibition |
title_short | IL-6 and IL-10 Anti-Inflammatory Activity Links Exercise to Hypothalamic Insulin and Leptin Sensitivity through IKKβ and ER Stress Inhibition |
title_sort | il-6 and il-10 anti-inflammatory activity links exercise to hypothalamic insulin and leptin sensitivity through ikkβ and er stress inhibition |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2927536/ https://www.ncbi.nlm.nih.gov/pubmed/20808781 http://dx.doi.org/10.1371/journal.pbio.1000465 |
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