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MAP3K8 (TPL2/COT) Affects Obesity-Induced Adipose Tissue Inflammation without Systemic Effects in Humans and in Mice
Chronic low-grade inflammation in adipose tissue often accompanies obesity, leading to insulin resistance and increasing the risk for metabolic diseases. MAP3K8 (TPL2/COT) is an important signal transductor and activator of pro-inflammatory pathways that has been linked to obesity-induced adipose ti...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3933658/ https://www.ncbi.nlm.nih.gov/pubmed/24586913 http://dx.doi.org/10.1371/journal.pone.0089615 |
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author | Ballak, Dov B. van Essen, Peter van Diepen, Janna A. Jansen, Henry Hijmans, Anneke Matsuguchi, Tetsuya Sparrer, Helmut Tack, Cees J. Netea, Mihai G. Joosten, Leo A. B. Stienstra, Rinke |
author_facet | Ballak, Dov B. van Essen, Peter van Diepen, Janna A. Jansen, Henry Hijmans, Anneke Matsuguchi, Tetsuya Sparrer, Helmut Tack, Cees J. Netea, Mihai G. Joosten, Leo A. B. Stienstra, Rinke |
author_sort | Ballak, Dov B. |
collection | PubMed |
description | Chronic low-grade inflammation in adipose tissue often accompanies obesity, leading to insulin resistance and increasing the risk for metabolic diseases. MAP3K8 (TPL2/COT) is an important signal transductor and activator of pro-inflammatory pathways that has been linked to obesity-induced adipose tissue inflammation. We used human adipose tissue biopsies to study the relationship of MAP3K8 expression with markers of obesity and expression of pro-inflammatory cytokines (IL-1β, IL-6 and IL-8). Moreover, we evaluated obesity-induced adipose tissue inflammation and insulin resistance in mice lacking MAP3K8 and WT mice on a high-fat diet (HFD) for 16 weeks. Individuals with a BMI >30 displayed a higher mRNA expression of MAP3K8 in adipose tissue compared to individuals with a normal BMI. Additionally, high mRNA expression levels of IL-1β, IL-6 and IL-8, but not TNF -α, in human adipose tissue were associated with higher expression of MAP3K8. Moreover, high plasma SAA and CRP did not associate with increased MAP3K8 expression in adipose tissue. Similarly, no association was found for MAP3K8 expression with plasma insulin or glucose levels. Mice lacking MAP3K8 had similar bodyweight gain as WT mice, yet displayed lower mRNA expression levels of IL-1β, IL-6 and CXCL1 in adipose tissue in response to the HFD as compared to WT animals. However, MAP3K8 deficient mice were not protected against HFD-induced adipose tissue macrophage infiltration or the development of insulin resistance. Together, the data in both human and mouse show that MAP3K8 is involved in local adipose tissue inflammation, specifically for IL-1β and its responsive cytokines IL-6 and IL-8, but does not seem to have systemic effects on insulin resistance. |
format | Online Article Text |
id | pubmed-3933658 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-39336582014-02-25 MAP3K8 (TPL2/COT) Affects Obesity-Induced Adipose Tissue Inflammation without Systemic Effects in Humans and in Mice Ballak, Dov B. van Essen, Peter van Diepen, Janna A. Jansen, Henry Hijmans, Anneke Matsuguchi, Tetsuya Sparrer, Helmut Tack, Cees J. Netea, Mihai G. Joosten, Leo A. B. Stienstra, Rinke PLoS One Research Article Chronic low-grade inflammation in adipose tissue often accompanies obesity, leading to insulin resistance and increasing the risk for metabolic diseases. MAP3K8 (TPL2/COT) is an important signal transductor and activator of pro-inflammatory pathways that has been linked to obesity-induced adipose tissue inflammation. We used human adipose tissue biopsies to study the relationship of MAP3K8 expression with markers of obesity and expression of pro-inflammatory cytokines (IL-1β, IL-6 and IL-8). Moreover, we evaluated obesity-induced adipose tissue inflammation and insulin resistance in mice lacking MAP3K8 and WT mice on a high-fat diet (HFD) for 16 weeks. Individuals with a BMI >30 displayed a higher mRNA expression of MAP3K8 in adipose tissue compared to individuals with a normal BMI. Additionally, high mRNA expression levels of IL-1β, IL-6 and IL-8, but not TNF -α, in human adipose tissue were associated with higher expression of MAP3K8. Moreover, high plasma SAA and CRP did not associate with increased MAP3K8 expression in adipose tissue. Similarly, no association was found for MAP3K8 expression with plasma insulin or glucose levels. Mice lacking MAP3K8 had similar bodyweight gain as WT mice, yet displayed lower mRNA expression levels of IL-1β, IL-6 and CXCL1 in adipose tissue in response to the HFD as compared to WT animals. However, MAP3K8 deficient mice were not protected against HFD-induced adipose tissue macrophage infiltration or the development of insulin resistance. Together, the data in both human and mouse show that MAP3K8 is involved in local adipose tissue inflammation, specifically for IL-1β and its responsive cytokines IL-6 and IL-8, but does not seem to have systemic effects on insulin resistance. Public Library of Science 2014-02-24 /pmc/articles/PMC3933658/ /pubmed/24586913 http://dx.doi.org/10.1371/journal.pone.0089615 Text en © 2014 Ballak 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 Ballak, Dov B. van Essen, Peter van Diepen, Janna A. Jansen, Henry Hijmans, Anneke Matsuguchi, Tetsuya Sparrer, Helmut Tack, Cees J. Netea, Mihai G. Joosten, Leo A. B. Stienstra, Rinke MAP3K8 (TPL2/COT) Affects Obesity-Induced Adipose Tissue Inflammation without Systemic Effects in Humans and in Mice |
title | MAP3K8 (TPL2/COT) Affects Obesity-Induced Adipose Tissue Inflammation without Systemic Effects in Humans and in Mice |
title_full | MAP3K8 (TPL2/COT) Affects Obesity-Induced Adipose Tissue Inflammation without Systemic Effects in Humans and in Mice |
title_fullStr | MAP3K8 (TPL2/COT) Affects Obesity-Induced Adipose Tissue Inflammation without Systemic Effects in Humans and in Mice |
title_full_unstemmed | MAP3K8 (TPL2/COT) Affects Obesity-Induced Adipose Tissue Inflammation without Systemic Effects in Humans and in Mice |
title_short | MAP3K8 (TPL2/COT) Affects Obesity-Induced Adipose Tissue Inflammation without Systemic Effects in Humans and in Mice |
title_sort | map3k8 (tpl2/cot) affects obesity-induced adipose tissue inflammation without systemic effects in humans and in mice |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3933658/ https://www.ncbi.nlm.nih.gov/pubmed/24586913 http://dx.doi.org/10.1371/journal.pone.0089615 |
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