Furthermore, obesity-mediated iNOS and nitric oxide cause insulin resistance by s-nitrosylating the IRE1α, which affects the ER homeostasis role by inhibiting the XBP1 splicing, but maintaining the IRE1α phosphorylation and c-Jun N-terminal kinase (JNK) activation and its mediated inflammation [238]. Here, MAPK8 is linked to obesity due to melanocortin 4 receptor deficiency.