Institute of Transport and Logistics Studies.  Faculty of Economics and Business. The University of Sydne

Ballak, D.B.

Diepen, J.A. van

Essen, P. van

Hijmans, A.G.

Jansen, H.J.

Joosten, L.A.B.

Matsuguchi, T.

Netea, M.G.

Sparrer, H.

Stienstra, R.

Tack, C.J.J.

PLoS ONE

English

PubMed

Bruijnes, Remco

Sydney eScholarship

Continental drift: connecting Great Britain and Scandinavia

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-1ß, 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-1ß, IL-6 and IL-8, but not TNF -a, 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-1ß, 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-1ß and its responsive cytokines IL-6 and IL-8, but does not seem to have systemic effects on insulin resistance

van Essen, P.

van Diepen, J.A.

Jansen, H.

Hijmans, A.

Tack, C.J.

Joosten, L.A.

NARCIS 

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 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-1beta, 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-1beta, IL-6 and IL-8, but not TNF -alpha, 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-1beta, 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-1beta and its responsive cytokines IL-6 and IL-8, but does not seem to have systemic effects on insulin resistance

Contains fulltext :
                  137391.pdf (publisher's version ) (Open Access)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-1beta, 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-1beta, IL-6 and IL-8, but not TNF -alpha, 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-1beta, 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-1beta and its responsive cytokines IL-6 and IL-8, but does not seem to have systemic effects on insulin resistance

Radboud Repository

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

Dov B Ballak

Peter van Essen

Janna A van Diepen

Henry Jansen

Anneke Hijmans

Tetsuya Matsuguchi

Helmut Sparrer

Cees J Tack

Mihai G Netea

Leo A B Joosten

Rinke Stienstra

Directory of Open Access Journals

MAP3K8 (TPL2/COT) affects obesity-induced adipose tissue inflammation without systemic effects in humans and in mice.

A serine/ threonine kinase, Cot/Tpl2, modulates bacterial DNA-induced IL-12 production and Th cell differentiation.

Activation of MEK-1 and SEK-1 by Tpl-2 proto-oncoprotein, a novel MAP kinase kinase kinase.

Cellular mechanisms of insulin resistance: role of stressregulated serine kinases and insulin receptor substrates (IRS) serine phosphorylation.

Differential regulation and properties of MAPKs.

Gut microbiota drives metabolic disease in immunologically altered mice.

How interleukin-1beta induces gouty arthritis.

Inflammatory Mechanisms in Obesity. Annu Rev Immunol.

Interleukin-1beta-induced insulin resistance in adipocytes through downregulation of insulin receptor substrate-1 expression.

Macrophages, inflammation, and insulin resistance.

Multiple mitogen-activated protein kinase signaling pathways connect the cot oncoprotein to the c-jun promoter and to cellular transformation.

Regulation and function of TPL-2, an IkappaB kinase-regulated MAP kinase kinase kinase.

The extracellular signal-regulated kinase isoform ERK1 is specifically required for in vitro and in vivo adipogenesis.

TNF-alpha induction by LPS is regulated posttranscriptionally via a Tpl2/ERKdependent pathway.

Tpl2 kinase is upregulated in adipose tissue in obesity and may mediate interleukin1beta and tumor necrosis factor-{alpha} effects on extracellular signal-regulated kinase activation and lipolysis.

Tpl2 kinase signal transduction in inflammation and cancer.

Tumor progression locus 2 (Map3k8) is critical for host defense against Listeria monocytogenes and IL-1 beta production.

Tumor progression locus 2 (Tpl2) deficiency does not protect against obesity-induced metabolic disease.

Tumor progression locus 2 (TPL2) regulates obesity-associated inflammation and insulin resistance.

Type 2 diabetes as an inflammatory disease.

http://repository.ubn.ru.nl/bitstream/2066/137391/1/137391.pdf

Continental drift: connecting Great Britain and Scandinavia

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Radboud Repository

Directory of Open Access Journals