Recently, several studies reported that specific inhibition of PPARγ phosphorylation, induced by “pathological stimuli” such as a high-fat diet, obesity, and inflammation, at serine 273 (S273) by TZD and synthetic ligands, resulted in alterations in gene expression profile which led to insulin resistance in animals and humans. Here, PPARG is linked to obesity due to melanocortin 4 receptor deficiency.