WSF-7 Inhibits Obesity-Mediated PPAR gamma Phosphorylation and Improves Insulin Sensitivity in 3T3-L1 Adipocytes

Peroxisome proliferator-activated receptor gamma (PPAR gamma), the molecular target for antidiabetic thiazolidinediones (TZDs), is a master regulator of preadipocyte differentiation and lipid metabolism. The adverse side effects of TZDs, arising from their potent agonistic activity, can be minimized by PPAR gamma partial agonists or PPAR gamma non-agonists without loss of insulin sensitization. In this study, we reported that WSF-7, a synthetic chemical derived from natural monoterpene alpha-pinene, is a partial PPAR gamma agonist. We found that WSF-7 binds directly to PPAR gamma. Activation of PPAR gamma by WSF-7 promotes adipogenesis, adiponectin oligomerization and insulin-induced glucose uptake. WSF-7 also inhibits obesity-mediated PPAR gamma phosphorylation at serine (Ser)273 and improves insulin sensitivity of 3T3-L1 adipocytes. Our study suggested that WSF-7 activates PPAR gamma transcription by a mechanism different from that of rosiglitazone or luteolin. Therefore, WSF-7 might be a potential therapeutic drug to treat type 2 diabetes.