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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2016
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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. |
format | Online Article Text |
id | pubmed-5049774 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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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