Fig. (3) A novel mechanism for PPAR-γ signaling? Obesity and high fat diet induce inflammation and cleavage of the p35 protein to generate p25. The p25 activates CDK5, which phosphorylates PPARγ on S273, thereby preventing the transcription of specific PPAR-γ targets (A, red box). The thiazolidinediones activate the full repertoire of PPARγ target genes via binding to the LBD. SPPARMs have positive effects (green) via blocking CDK5 and stimulating a discrete number of PPAR-γ responses (A, red box) through binding to LBD.