Activation of Peroxisome Proliferator–Activated Receptor-b/-d (PPAR-b/-d) Ameliorates Insulin Signaling and Reduces SOCS3 Levels by Inhibiting

OBJECTIVE—It has been suggested that interleukin (IL)-6 is one of the mediators linking obesity-derived chronic inflammation with insulin resistance through activation of STAT3, with subsequent upregulation of suppressor of cytokine signaling 3 (SOCS3). We evaluated whether peroxisome proliferator–activated receptor (PPAR)-b/-d prevented activation of the IL-6-STAT3-SOCS3 path-way and insulin resistance in adipocytes. RESEARCH DESIGN AND METHODS—Adipocytes and white adipose tissue from wild-type and PPAR-b/-d-null mice were used to evaluate the effect of PPAR-b/-d on the IL-6-STAT3-SOCS3 pathway. RESULTS—First, we observed that the PPAR-b/-d agonist GW501516 prevented both IL-6–dependent reduction in insulin-stimulated Akt phosphorylation and glucose uptake in adipocytes. In addition, this drug treatment abolished IL-6–induced SOCS