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Inhibition of NET Release Fails to Reduce Adipose Tissue Inflammation in Mice

Obesity-associated diseases such as Type 2 diabetes, liver disease and cardiovascular diseases are profoundly mediated by low-grade chronic inflammation of the adipose tissue. Recently, the importance of neutrophils and neutrophil-derived myeloperoxidase and neutrophil elastase on the induction of i...

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Autores principales: Braster, Quinte, Silvestre Roig, Carlos, Hartwig, Helene, Beckers, Linda, den Toom, Myrthe, Döring, Yvonne, Daemen, Mat J., Lutgens, Esther, Soehnlein, Oliver
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5049774/
https://www.ncbi.nlm.nih.gov/pubmed/27701440
http://dx.doi.org/10.1371/journal.pone.0163922
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author Braster, Quinte
Silvestre Roig, Carlos
Hartwig, Helene
Beckers, Linda
den Toom, Myrthe
Döring, Yvonne
Daemen, Mat J.
Lutgens, Esther
Soehnlein, Oliver
author_facet Braster, Quinte
Silvestre Roig, Carlos
Hartwig, Helene
Beckers, Linda
den Toom, Myrthe
Döring, Yvonne
Daemen, Mat J.
Lutgens, Esther
Soehnlein, Oliver
author_sort Braster, Quinte
collection PubMed
description Obesity-associated diseases such as Type 2 diabetes, liver disease and cardiovascular diseases are profoundly mediated by low-grade chronic inflammation of the adipose tissue. Recently, the importance of neutrophils and neutrophil-derived myeloperoxidase and neutrophil elastase on the induction of insulin resistance has been established. Since neutrophil elastase and myeloperoxidase are critically involved in the release of neutrophil extracellular traps (NETs), we here hypothesized that NETs may be relevant to early adipose tissue inflammation. Thus, we tested the effect of the Peptidyl Arginine Deiminase 4 inhibitor Cl-amidine, a compound preventing histone citrullination and subsequent NET release, in a mouse model of adipose tissue inflammation. C57BL6 mice received a 60% high fat diet for 10 weeks and were treated with either Cl-amidine or vehicle. Flow cytometry of adipose tissue and liver, immunohistological analysis and glucose and insulin tolerance tests were performed to determine the effect of the treatment and diet. Although high fat diet feeding induced insulin resistance no significant effect was observed between the treatment groups. In addition no effect was found in leukocyte infiltration and activation in the adipose tissue and liver. Therefore we concluded that inhibition of neutrophil extracellular trap formation may have no clinical relevance for early obesity-mediated pathogenesis of the adipose tissue and liver.
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spelling pubmed-50497742016-10-27 Inhibition of NET Release Fails to Reduce Adipose Tissue Inflammation in Mice Braster, Quinte Silvestre Roig, Carlos Hartwig, Helene Beckers, Linda den Toom, Myrthe Döring, Yvonne Daemen, Mat J. Lutgens, Esther Soehnlein, Oliver PLoS One Research Article Obesity-associated diseases such as Type 2 diabetes, liver disease and cardiovascular diseases are profoundly mediated by low-grade chronic inflammation of the adipose tissue. Recently, the importance of neutrophils and neutrophil-derived myeloperoxidase and neutrophil elastase on the induction of insulin resistance has been established. Since neutrophil elastase and myeloperoxidase are critically involved in the release of neutrophil extracellular traps (NETs), we here hypothesized that NETs may be relevant to early adipose tissue inflammation. Thus, we tested the effect of the Peptidyl Arginine Deiminase 4 inhibitor Cl-amidine, a compound preventing histone citrullination and subsequent NET release, in a mouse model of adipose tissue inflammation. C57BL6 mice received a 60% high fat diet for 10 weeks and were treated with either Cl-amidine or vehicle. Flow cytometry of adipose tissue and liver, immunohistological analysis and glucose and insulin tolerance tests were performed to determine the effect of the treatment and diet. Although high fat diet feeding induced insulin resistance no significant effect was observed between the treatment groups. In addition no effect was found in leukocyte infiltration and activation in the adipose tissue and liver. Therefore we concluded that inhibition of neutrophil extracellular trap formation may have no clinical relevance for early obesity-mediated pathogenesis of the adipose tissue and liver. Public Library of Science 2016-10-04 /pmc/articles/PMC5049774/ /pubmed/27701440 http://dx.doi.org/10.1371/journal.pone.0163922 Text en © 2016 Braster 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 (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Braster, Quinte
Silvestre Roig, Carlos
Hartwig, Helene
Beckers, Linda
den Toom, Myrthe
Döring, Yvonne
Daemen, Mat J.
Lutgens, Esther
Soehnlein, Oliver
Inhibition of NET Release Fails to Reduce Adipose Tissue Inflammation in Mice
title Inhibition of NET Release Fails to Reduce Adipose Tissue Inflammation in Mice
title_full Inhibition of NET Release Fails to Reduce Adipose Tissue Inflammation in Mice
title_fullStr Inhibition of NET Release Fails to Reduce Adipose Tissue Inflammation in Mice
title_full_unstemmed Inhibition of NET Release Fails to Reduce Adipose Tissue Inflammation in Mice
title_short Inhibition of NET Release Fails to Reduce Adipose Tissue Inflammation in Mice
title_sort inhibition of net release fails to reduce adipose tissue inflammation in mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5049774/
https://www.ncbi.nlm.nih.gov/pubmed/27701440
http://dx.doi.org/10.1371/journal.pone.0163922
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