Figure 3.

Potential of the newly identified TZD mechanism to explain the pleotropic “insulin sensitizer” pharmacology. Rewiring metabolism by slowing the entry of pyruvate into the mitochondrion alters the inflammatory response in multiple cell types with implications to chronic disease and response to environmental challenges such as viral infection. The general schematic of pathways that are involved is shown here. While many transcriptional networks are clearly involved, there has been a focus on PPARγ, since it is a master regulator of both adipose differentiation and the attenuation of the inflammatory response, both of which are known to be an important part of the TZD pharmacology.