Regulation of PPARγ activity in conditions of a standard diet (lean, insulin-sensitive state) compared to a high-fat diet (obese, insulin-resistant state) in WAT of mice. The activity of PPARγ is differentially regulated during standard diet (left) and high-fat diet (right) conditions. Obesity and insulin resistance, both a result of a high-fat diet, lead to the production of inflammatory cytokines, such as TNFα. Both FFA and TNFα can activate CDK5, which in turn phosphorylates serine 273 on PPARγ thereby inducing the expression of different gene family sets compared to unphosphorylated PPARγ. Differential induction and repression of gene sets are represented by A, B, and C. Furthermore, some PPARγ ligands block the phosphorylation of PPARγ by CDK5, which may result in the expression of the same gene family as under a normal diet. Abbreviations: CDK5, cyclin-dependent kinase 5; FFA, free fatty acids; PPARγ, peroxisome proliferator-activated receptor γ; TNFα, tumor necrosis factor α.