Nonetheless, our results demonstrate that myeloid JNK1 plays a role in the regulation of cytokine expression in adipose tissue and the development of insulin resistance in type 2 diabetes, however, it does not appear to be the driver of this phenotype at earlier stages of obesity and insulin resistance, supporting the concept that metabolic target cells are likely to provide the initial inflammatory and/or stress signals that result in metabolic deterioration and their involvement is paramount to metabolic disease. Here, MAPK8 is linked to obesity due to melanocortin 4 receptor deficiency.