Fig. 2. Mechanism by which of PPARγ ligands regulate insulin sensitivity. In adipose tissue (AT), activation of PPARγ by thiazolidinedione (TZD) modulates glucose and lipid metabolism. PPARγ also regulates the levels of adipokines, such as adiponectin, TNF-α, MCP-1, and resistin. As a result of reduced free fatty acid levels in circulation and changed adipokine profiles, insulin sensitivity is improved, which is also mediated by suppressing glucose production in the liver, stimulating glucose uptake in skeletal muscle and AT, and promoting insulin secretion in the pancreas. Furthermore, activation of PPARγ by TZDs also suppresses macrophage infiltration into AT and induces polarization into an anti-inflammatory M2 phenotype.