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Insulin Resistance is Associated with MCP1-Mediated Macrophage Accumulation in Skeletal Muscle in Mice and Humans

Inflammation is now recognized as a major factor contributing to type 2 diabetes (T2D). However, while the mechanisms and consequences associated with white adipose tissue inflammation are well described, very little is known concerning the situation in skeletal muscle. The aim of this study was to...

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Autores principales: Patsouris, David, Cao, Jingwei-Ji, Vial, Guillaume, Bravard, Amelie, Lefai, Etienne, Durand, Annie, Durand, Christine, Chauvin, Marie-Agnés, Laugerette, Fabienne, Debard, Cyrille, Michalski, Marie-Caroline, Laville, Martine, Vidal, Hubert, Rieusset, Jennifer
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4206428/
https://www.ncbi.nlm.nih.gov/pubmed/25337938
http://dx.doi.org/10.1371/journal.pone.0110653
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author Patsouris, David
Cao, Jingwei-Ji
Vial, Guillaume
Bravard, Amelie
Lefai, Etienne
Durand, Annie
Durand, Christine
Chauvin, Marie-Agnés
Laugerette, Fabienne
Debard, Cyrille
Michalski, Marie-Caroline
Laville, Martine
Vidal, Hubert
Rieusset, Jennifer
author_facet Patsouris, David
Cao, Jingwei-Ji
Vial, Guillaume
Bravard, Amelie
Lefai, Etienne
Durand, Annie
Durand, Christine
Chauvin, Marie-Agnés
Laugerette, Fabienne
Debard, Cyrille
Michalski, Marie-Caroline
Laville, Martine
Vidal, Hubert
Rieusset, Jennifer
author_sort Patsouris, David
collection PubMed
description Inflammation is now recognized as a major factor contributing to type 2 diabetes (T2D). However, while the mechanisms and consequences associated with white adipose tissue inflammation are well described, very little is known concerning the situation in skeletal muscle. The aim of this study was to investigate, in vitro and in vivo, how skeletal muscle inflammation develops and how in turn it modulates local and systemic insulin sensitivity in different mice models of T2D and in humans, focusing on the role of the chemokine MCP1. Here, we found that skeletal muscle inflammation and macrophage markers are increased and associated with insulin resistance in mice models and humans. In addition, we demonstrated that intra-muscular TNFα expression is exclusively restricted to the population of intramuscular leukocytes and that the chemokine MCP1 was associated with skeletal muscle inflammatory markers in these models. Furthermore, we demonstrated that exposure of C2C12 myotubes to palmitate elevated the production of the chemokine MCP1 and that the muscle-specific overexpression of MCP1 in transgenic mice induced the local recruitment of macrophages and altered local insulin sensitivity. Overall our study demonstrates that skeletal muscle inflammation is clearly increased in the context of T2D in each one of the models we investigated, which is likely consecutive to the lipotoxic environment generated by peripheral insulin resistance, further increasing MCP1 expression in muscle. Consequently, our results suggest that MCP1-mediated skeletal muscle macrophages recruitment plays a role in the etiology of T2D.
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spelling pubmed-42064282014-10-27 Insulin Resistance is Associated with MCP1-Mediated Macrophage Accumulation in Skeletal Muscle in Mice and Humans Patsouris, David Cao, Jingwei-Ji Vial, Guillaume Bravard, Amelie Lefai, Etienne Durand, Annie Durand, Christine Chauvin, Marie-Agnés Laugerette, Fabienne Debard, Cyrille Michalski, Marie-Caroline Laville, Martine Vidal, Hubert Rieusset, Jennifer PLoS One Research Article Inflammation is now recognized as a major factor contributing to type 2 diabetes (T2D). However, while the mechanisms and consequences associated with white adipose tissue inflammation are well described, very little is known concerning the situation in skeletal muscle. The aim of this study was to investigate, in vitro and in vivo, how skeletal muscle inflammation develops and how in turn it modulates local and systemic insulin sensitivity in different mice models of T2D and in humans, focusing on the role of the chemokine MCP1. Here, we found that skeletal muscle inflammation and macrophage markers are increased and associated with insulin resistance in mice models and humans. In addition, we demonstrated that intra-muscular TNFα expression is exclusively restricted to the population of intramuscular leukocytes and that the chemokine MCP1 was associated with skeletal muscle inflammatory markers in these models. Furthermore, we demonstrated that exposure of C2C12 myotubes to palmitate elevated the production of the chemokine MCP1 and that the muscle-specific overexpression of MCP1 in transgenic mice induced the local recruitment of macrophages and altered local insulin sensitivity. Overall our study demonstrates that skeletal muscle inflammation is clearly increased in the context of T2D in each one of the models we investigated, which is likely consecutive to the lipotoxic environment generated by peripheral insulin resistance, further increasing MCP1 expression in muscle. Consequently, our results suggest that MCP1-mediated skeletal muscle macrophages recruitment plays a role in the etiology of T2D. Public Library of Science 2014-10-22 /pmc/articles/PMC4206428/ /pubmed/25337938 http://dx.doi.org/10.1371/journal.pone.0110653 Text en © 2014 Patsouris et al http://creativecommons.org/licenses/by/4.0/ 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 properly credited.
spellingShingle Research Article
Patsouris, David
Cao, Jingwei-Ji
Vial, Guillaume
Bravard, Amelie
Lefai, Etienne
Durand, Annie
Durand, Christine
Chauvin, Marie-Agnés
Laugerette, Fabienne
Debard, Cyrille
Michalski, Marie-Caroline
Laville, Martine
Vidal, Hubert
Rieusset, Jennifer
Insulin Resistance is Associated with MCP1-Mediated Macrophage Accumulation in Skeletal Muscle in Mice and Humans
title Insulin Resistance is Associated with MCP1-Mediated Macrophage Accumulation in Skeletal Muscle in Mice and Humans
title_full Insulin Resistance is Associated with MCP1-Mediated Macrophage Accumulation in Skeletal Muscle in Mice and Humans
title_fullStr Insulin Resistance is Associated with MCP1-Mediated Macrophage Accumulation in Skeletal Muscle in Mice and Humans
title_full_unstemmed Insulin Resistance is Associated with MCP1-Mediated Macrophage Accumulation in Skeletal Muscle in Mice and Humans
title_short Insulin Resistance is Associated with MCP1-Mediated Macrophage Accumulation in Skeletal Muscle in Mice and Humans
title_sort insulin resistance is associated with mcp1-mediated macrophage accumulation in skeletal muscle in mice and humans
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4206428/
https://www.ncbi.nlm.nih.gov/pubmed/25337938
http://dx.doi.org/10.1371/journal.pone.0110653
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