IRS1 and obesity due to melanocortin 4 receptor deficiency: Obesity can induce activation of IKKβ, leading to nuclear translocation of NF-κB and, as a result, the production of various inflammatory markers and potential mediators, and obesity can also co-promote phosphorylation of IRS1 at serine sites (ser302 and ser307) through JNK activation, which together leads to the development of IR (74).