Recent studies have revealed that specific phosphorylation of S273 on PPARγ by obesity-linked or high-fat-diet-induced activation of CDK5, which leads to insulin resistance in animals and humans, can be ameliorated by treatment with TZDs or ligands without transactivation of PPARγ via inhibition of CDK5-mediated S273 phosphorylation [11, 14]. The gene discussed is CDK5; the disease is obesity due to melanocortin 4 receptor deficiency.