NOS2 and obesity due to melanocortin 4 receptor deficiency: The reported progressive decline in hepatic XBP1 post-transcriptional splicing has been mainly attributed to an increase in IRE1α S-nitrosylation and depleted endoribonuclease activity mediated by elevated inducible nitric oxide synthase (iNOS) activity, during metaflammation characteristic of metabolic syndrome and obesity (76).