INS and obesity due to melanocortin 4 receptor deficiency: Choi et al. reported in 2010 that cyclin-dependent kinase 5- (CDK5-) stimulated phosphorylation at serine 273 of PPARγ (pSer273PPARγ), which led to the dysregulated expression of a set of genes in adipose tissue, especially the epididymal white fat tissue (eWAT), was the critical link between obesity and IR, and pSer273PPARγ inhibition rather than PPARγ agonism was responsible for the insulin-sensitizing and antidiabetic effects of PPARγ agonists [27, 28].