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.