ArticlePloS one2014
MAP3K8 (TPL2/COT) affects obesity-induced adipose tissue inflammation without systemic effects in humans and in mice.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 20 citations in OpenAlex.
- Insights into the molecular and genetic role of obesity in breast cancer pathogenesis.Cancer biology & therapy · 2025Review
- A narrative review: CXC chemokines influence immune surveillance in obesity and obesity-related diseases: Type 2 diabetes and nonalcoholic fatty liver disease.Reviews in endocrine & metabolic disorders · 2023Review
- Transcriptomic analysis of LMH cells in response to the overexpression of a protein ofFrontiers in veterinary science · 2022Article
- Novel role of circRSU1 in the progression of osteoarthritis by adjusting oxidative stress.Theranostics · 2021Article
- Sarcopenic Obesity, Insulin Resistance, and Their Implications in Cardiovascular and Metabolic Consequences.International journal of molecular sciences · 2020Review
- Comparison of visceral adipose tissue DNA methylation and gene expression profiles in female adolescents with obesity.Diabetology & metabolic syndrome · 2019Article
- Alanine Aminotransferase and Body Composition in Obese Men and Women.Disease markers · 2019Article
- ASK1 (MAP3K5) is transcriptionally upregulated by E2F1 in adipose tissue in obesity, molecularly defining a human dys-metabolic obese phenotype.Molecular metabolism · 2017Article
- Tpl2 promotes neutrophil trafficking, oxidative burst, and bacterial killing.Journal of leukocyte biology · 2017Article
- Dysregulated expression of microRNAs and mRNAs in pulmonary artery remodeling in ascites syndrome in broiler chickens.Oncotarget · 2017Article
- The Tpl2 Kinase Regulates the COX-2/Prostaglandin E2 Axis in Adipocytes in Inflammatory Conditions.Molecular endocrinology (Baltimore, Md.) · 2015Article
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
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Abstract
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.
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