Cargando…

The Dual-Specificity Phosphatase 2 (DUSP2) Does Not Regulate Obesity-Associated Inflammation or Insulin Resistance in Mice

Alterations in the immune cell profile and the induction of inflammation within adipose tissue are a hallmark of obesity in mice and humans. Dual-specificity phosphatase 2 (DUSP2) is widely expressed within the immune system and plays a key role promoting immune and inflammatory responses dependent...

Descripción completa

Detalles Bibliográficos
Autores principales: Lancaster, Graeme I., Kraakman, Michael J., Kammoun, Helene L., Langley, Katherine G., Estevez, Emma, Banerjee, Ashish, Grumont, Raelene J., Febbraio, Mark A., Gerondakis, Steve
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222916/
https://www.ncbi.nlm.nih.gov/pubmed/25375135
http://dx.doi.org/10.1371/journal.pone.0111524
_version_ 1782343134641913856
author Lancaster, Graeme I.
Kraakman, Michael J.
Kammoun, Helene L.
Langley, Katherine G.
Estevez, Emma
Banerjee, Ashish
Grumont, Raelene J.
Febbraio, Mark A.
Gerondakis, Steve
author_facet Lancaster, Graeme I.
Kraakman, Michael J.
Kammoun, Helene L.
Langley, Katherine G.
Estevez, Emma
Banerjee, Ashish
Grumont, Raelene J.
Febbraio, Mark A.
Gerondakis, Steve
author_sort Lancaster, Graeme I.
collection PubMed
description Alterations in the immune cell profile and the induction of inflammation within adipose tissue are a hallmark of obesity in mice and humans. Dual-specificity phosphatase 2 (DUSP2) is widely expressed within the immune system and plays a key role promoting immune and inflammatory responses dependent on mitogen-activated protein kinase (MAPK) activity. We hypothesised that the absence of DUSP2 would protect mice against obesity-associated inflammation and insulin resistance. Accordingly, male and female littermate mice that are either wild-type (wt) or homozygous for a germ-line null mutation of the dusp2 gene (dusp2(−/−)) were fed either a standard chow diet (SCD) or high fat diet (HFD) for 12 weeks prior to metabolic phenotyping. Compared with mice fed the SCD, all mice consuming the HFD became obese, developed glucose intolerance and insulin resistance, and displayed increased macrophage recruitment and markers of inflammation in epididymal white adipose tissue. The absence of DUSP2, however, had no effect on the development of obesity or adipose tissue inflammation. Whole body insulin sensitivity in male mice was unaffected by an absence of DUSP2 in response to either the SCD or HFD; however, HFD-induced insulin resistance was slightly, but significantly, reduced in female dusp2(−/−) mice. In conclusion, DUSP2 plays no role in regulating obesity-associated inflammation and only a minor role in controlling insulin sensitivity following HFD in female, but not male, mice. These data indicate that rather than DUSP2 being a pan regulator of MAPK dependent immune cell mediated inflammation, it appears to differentially regulate inflammatory responses that have a MAPK component.
format Online
Article
Text
id pubmed-4222916
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-42229162014-11-13 The Dual-Specificity Phosphatase 2 (DUSP2) Does Not Regulate Obesity-Associated Inflammation or Insulin Resistance in Mice Lancaster, Graeme I. Kraakman, Michael J. Kammoun, Helene L. Langley, Katherine G. Estevez, Emma Banerjee, Ashish Grumont, Raelene J. Febbraio, Mark A. Gerondakis, Steve PLoS One Research Article Alterations in the immune cell profile and the induction of inflammation within adipose tissue are a hallmark of obesity in mice and humans. Dual-specificity phosphatase 2 (DUSP2) is widely expressed within the immune system and plays a key role promoting immune and inflammatory responses dependent on mitogen-activated protein kinase (MAPK) activity. We hypothesised that the absence of DUSP2 would protect mice against obesity-associated inflammation and insulin resistance. Accordingly, male and female littermate mice that are either wild-type (wt) or homozygous for a germ-line null mutation of the dusp2 gene (dusp2(−/−)) were fed either a standard chow diet (SCD) or high fat diet (HFD) for 12 weeks prior to metabolic phenotyping. Compared with mice fed the SCD, all mice consuming the HFD became obese, developed glucose intolerance and insulin resistance, and displayed increased macrophage recruitment and markers of inflammation in epididymal white adipose tissue. The absence of DUSP2, however, had no effect on the development of obesity or adipose tissue inflammation. Whole body insulin sensitivity in male mice was unaffected by an absence of DUSP2 in response to either the SCD or HFD; however, HFD-induced insulin resistance was slightly, but significantly, reduced in female dusp2(−/−) mice. In conclusion, DUSP2 plays no role in regulating obesity-associated inflammation and only a minor role in controlling insulin sensitivity following HFD in female, but not male, mice. These data indicate that rather than DUSP2 being a pan regulator of MAPK dependent immune cell mediated inflammation, it appears to differentially regulate inflammatory responses that have a MAPK component. Public Library of Science 2014-11-06 /pmc/articles/PMC4222916/ /pubmed/25375135 http://dx.doi.org/10.1371/journal.pone.0111524 Text en © 2014 Lancaster 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
Lancaster, Graeme I.
Kraakman, Michael J.
Kammoun, Helene L.
Langley, Katherine G.
Estevez, Emma
Banerjee, Ashish
Grumont, Raelene J.
Febbraio, Mark A.
Gerondakis, Steve
The Dual-Specificity Phosphatase 2 (DUSP2) Does Not Regulate Obesity-Associated Inflammation or Insulin Resistance in Mice
title The Dual-Specificity Phosphatase 2 (DUSP2) Does Not Regulate Obesity-Associated Inflammation or Insulin Resistance in Mice
title_full The Dual-Specificity Phosphatase 2 (DUSP2) Does Not Regulate Obesity-Associated Inflammation or Insulin Resistance in Mice
title_fullStr The Dual-Specificity Phosphatase 2 (DUSP2) Does Not Regulate Obesity-Associated Inflammation or Insulin Resistance in Mice
title_full_unstemmed The Dual-Specificity Phosphatase 2 (DUSP2) Does Not Regulate Obesity-Associated Inflammation or Insulin Resistance in Mice
title_short The Dual-Specificity Phosphatase 2 (DUSP2) Does Not Regulate Obesity-Associated Inflammation or Insulin Resistance in Mice
title_sort dual-specificity phosphatase 2 (dusp2) does not regulate obesity-associated inflammation or insulin resistance in mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222916/
https://www.ncbi.nlm.nih.gov/pubmed/25375135
http://dx.doi.org/10.1371/journal.pone.0111524
work_keys_str_mv AT lancastergraemei thedualspecificityphosphatase2dusp2doesnotregulateobesityassociatedinflammationorinsulinresistanceinmice
AT kraakmanmichaelj thedualspecificityphosphatase2dusp2doesnotregulateobesityassociatedinflammationorinsulinresistanceinmice
AT kammounhelenel thedualspecificityphosphatase2dusp2doesnotregulateobesityassociatedinflammationorinsulinresistanceinmice
AT langleykatherineg thedualspecificityphosphatase2dusp2doesnotregulateobesityassociatedinflammationorinsulinresistanceinmice
AT estevezemma thedualspecificityphosphatase2dusp2doesnotregulateobesityassociatedinflammationorinsulinresistanceinmice
AT banerjeeashish thedualspecificityphosphatase2dusp2doesnotregulateobesityassociatedinflammationorinsulinresistanceinmice
AT grumontraelenej thedualspecificityphosphatase2dusp2doesnotregulateobesityassociatedinflammationorinsulinresistanceinmice
AT febbraiomarka thedualspecificityphosphatase2dusp2doesnotregulateobesityassociatedinflammationorinsulinresistanceinmice
AT gerondakissteve thedualspecificityphosphatase2dusp2doesnotregulateobesityassociatedinflammationorinsulinresistanceinmice
AT lancastergraemei dualspecificityphosphatase2dusp2doesnotregulateobesityassociatedinflammationorinsulinresistanceinmice
AT kraakmanmichaelj dualspecificityphosphatase2dusp2doesnotregulateobesityassociatedinflammationorinsulinresistanceinmice
AT kammounhelenel dualspecificityphosphatase2dusp2doesnotregulateobesityassociatedinflammationorinsulinresistanceinmice
AT langleykatherineg dualspecificityphosphatase2dusp2doesnotregulateobesityassociatedinflammationorinsulinresistanceinmice
AT estevezemma dualspecificityphosphatase2dusp2doesnotregulateobesityassociatedinflammationorinsulinresistanceinmice
AT banerjeeashish dualspecificityphosphatase2dusp2doesnotregulateobesityassociatedinflammationorinsulinresistanceinmice
AT grumontraelenej dualspecificityphosphatase2dusp2doesnotregulateobesityassociatedinflammationorinsulinresistanceinmice
AT febbraiomarka dualspecificityphosphatase2dusp2doesnotregulateobesityassociatedinflammationorinsulinresistanceinmice
AT gerondakissteve dualspecificityphosphatase2dusp2doesnotregulateobesityassociatedinflammationorinsulinresistanceinmice