Does Pro¹²Ala Polymorphism Enhance the Physiological Role of PPAR𝜸2?

Figure 1

PPAR𝛾 transduction pathway. PPAR𝛾 has several extracellular and intracellular ligands that include dietary and bioactive lipids. Given its antidiabetogenic role, some PPAR𝛾 ligands include antidiabetic drugs such as thiazolidinediones. PPAR𝛾 is also modulated by several growth factor transduction pathways such as Jnk/Erk/MKP. It is also known that cyclin-dependent kinase 5 (Cdk5) bond to p25 (a product of the cleavage of p35 in obesity environment) inhibits PPAR𝛾 pathway by its phosphorylation. As a transcriptional factor, PPAR𝛾 binds to RXR (retinol X receptor) in order to transcribe several genes related to adipocyte differentiation and lipid storage in adipose tissue and increase insulin sensitivity in peripheral tissues by indirect increase of AMP kinase activity as well as several other antidiabetogenic effects. Moreover, PPAR𝛾 blocks NF𝜅B signaling, thus reducing proinflammatory cytokines and inflammation.