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Exercise Counterbalances Rho/ROCK2 Signaling Impairment in the Skeletal Muscle and Ameliorates Insulin Sensitivity in Obese Mice

Physical exercise is considered a fundamental strategy in improving insulin sensitivity and glucose uptake in skeletal muscle. However, the molecular mechanisms underlying this regulation, primarily on skeletal muscle glucose uptake, are not fully understood. Recent evidence has shown that Rho-kinas...

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Autores principales: Muñoz, Vitor R., Gaspar, Rafael C., Severino, Matheus B., Macêdo, Ana P. A., Simabuco, Fernando M., Ropelle, Eduardo R., Cintra, Dennys E., da Silva, Adelino S. R., Kim, Young-Bum, Pauli, José Rodrigo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256841/
https://www.ncbi.nlm.nih.gov/pubmed/34234788
http://dx.doi.org/10.3389/fimmu.2021.702025
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author Muñoz, Vitor R.
Gaspar, Rafael C.
Severino, Matheus B.
Macêdo, Ana P. A.
Simabuco, Fernando M.
Ropelle, Eduardo R.
Cintra, Dennys E.
da Silva, Adelino S. R.
Kim, Young-Bum
Pauli, José Rodrigo
author_facet Muñoz, Vitor R.
Gaspar, Rafael C.
Severino, Matheus B.
Macêdo, Ana P. A.
Simabuco, Fernando M.
Ropelle, Eduardo R.
Cintra, Dennys E.
da Silva, Adelino S. R.
Kim, Young-Bum
Pauli, José Rodrigo
author_sort Muñoz, Vitor R.
collection PubMed
description Physical exercise is considered a fundamental strategy in improving insulin sensitivity and glucose uptake in skeletal muscle. However, the molecular mechanisms underlying this regulation, primarily on skeletal muscle glucose uptake, are not fully understood. Recent evidence has shown that Rho-kinase (ROCK) isoforms play a pivotal role in regulating skeletal muscle glucose uptake and systemic glucose homeostasis. The current study evaluated the effect of physical exercise on ROCK2 signaling in skeletal muscle of insulin-resistant obese animals. Physiological (ITT) and molecular analysis (immunoblotting, and RT-qPCR) were performed. The contents of RhoA and ROCK2 protein were decreased in skeletal muscle of obese mice compared to control mice but were restored to normal levels in response to physical exercise. The exercised animals also showed higher phosphorylation of insulin receptor substrate 1 (IRS1 Serine 632/635) and protein kinase B (Akt) in the skeletal muscle. However, phosphatase and tensin homolog (PTEN) and protein-tyrosine phosphatase-1B (PTP-1B), both inhibitory regulators for insulin action, were increased in obesity but decreased after exercise. The impact of ROCK2 action on muscle insulin signaling is further underscored by the fact that impaired IRS1 and Akt phosphorylation caused by palmitate in C2C12 myotubes was entirely restored by ROCK2 overexpression. These results suggest that the exercise-induced upregulation of RhoA-ROCK2 signaling in skeletal muscle is associated with increased systemic insulin sensitivity in obese mice and further implicate that muscle ROCK2 could be a potential target for treating obesity-linked metabolic disorders.
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spelling pubmed-82568412021-07-06 Exercise Counterbalances Rho/ROCK2 Signaling Impairment in the Skeletal Muscle and Ameliorates Insulin Sensitivity in Obese Mice Muñoz, Vitor R. Gaspar, Rafael C. Severino, Matheus B. Macêdo, Ana P. A. Simabuco, Fernando M. Ropelle, Eduardo R. Cintra, Dennys E. da Silva, Adelino S. R. Kim, Young-Bum Pauli, José Rodrigo Front Immunol Immunology Physical exercise is considered a fundamental strategy in improving insulin sensitivity and glucose uptake in skeletal muscle. However, the molecular mechanisms underlying this regulation, primarily on skeletal muscle glucose uptake, are not fully understood. Recent evidence has shown that Rho-kinase (ROCK) isoforms play a pivotal role in regulating skeletal muscle glucose uptake and systemic glucose homeostasis. The current study evaluated the effect of physical exercise on ROCK2 signaling in skeletal muscle of insulin-resistant obese animals. Physiological (ITT) and molecular analysis (immunoblotting, and RT-qPCR) were performed. The contents of RhoA and ROCK2 protein were decreased in skeletal muscle of obese mice compared to control mice but were restored to normal levels in response to physical exercise. The exercised animals also showed higher phosphorylation of insulin receptor substrate 1 (IRS1 Serine 632/635) and protein kinase B (Akt) in the skeletal muscle. However, phosphatase and tensin homolog (PTEN) and protein-tyrosine phosphatase-1B (PTP-1B), both inhibitory regulators for insulin action, were increased in obesity but decreased after exercise. The impact of ROCK2 action on muscle insulin signaling is further underscored by the fact that impaired IRS1 and Akt phosphorylation caused by palmitate in C2C12 myotubes was entirely restored by ROCK2 overexpression. These results suggest that the exercise-induced upregulation of RhoA-ROCK2 signaling in skeletal muscle is associated with increased systemic insulin sensitivity in obese mice and further implicate that muscle ROCK2 could be a potential target for treating obesity-linked metabolic disorders. Frontiers Media S.A. 2021-06-21 /pmc/articles/PMC8256841/ /pubmed/34234788 http://dx.doi.org/10.3389/fimmu.2021.702025 Text en Copyright © 2021 Muñoz, Gaspar, Severino, Macêdo, Simabuco, Ropelle, Cintra, da Silva, Kim and Pauli https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Muñoz, Vitor R.
Gaspar, Rafael C.
Severino, Matheus B.
Macêdo, Ana P. A.
Simabuco, Fernando M.
Ropelle, Eduardo R.
Cintra, Dennys E.
da Silva, Adelino S. R.
Kim, Young-Bum
Pauli, José Rodrigo
Exercise Counterbalances Rho/ROCK2 Signaling Impairment in the Skeletal Muscle and Ameliorates Insulin Sensitivity in Obese Mice
title Exercise Counterbalances Rho/ROCK2 Signaling Impairment in the Skeletal Muscle and Ameliorates Insulin Sensitivity in Obese Mice
title_full Exercise Counterbalances Rho/ROCK2 Signaling Impairment in the Skeletal Muscle and Ameliorates Insulin Sensitivity in Obese Mice
title_fullStr Exercise Counterbalances Rho/ROCK2 Signaling Impairment in the Skeletal Muscle and Ameliorates Insulin Sensitivity in Obese Mice
title_full_unstemmed Exercise Counterbalances Rho/ROCK2 Signaling Impairment in the Skeletal Muscle and Ameliorates Insulin Sensitivity in Obese Mice
title_short Exercise Counterbalances Rho/ROCK2 Signaling Impairment in the Skeletal Muscle and Ameliorates Insulin Sensitivity in Obese Mice
title_sort exercise counterbalances rho/rock2 signaling impairment in the skeletal muscle and ameliorates insulin sensitivity in obese mice
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256841/
https://www.ncbi.nlm.nih.gov/pubmed/34234788
http://dx.doi.org/10.3389/fimmu.2021.702025
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