A novel PPARα/γ agonist, propane-2-sulfonic acid octadec-9-enyl-amide, ameliorates insulin resistance and gluconeogenesis in vivo and vitro

Peroxisome proliferator-activated receptor alpha/gamma (PPAR alpha/gamma) agonists have emerged as important pharmacological agents for improving insulin action. Propane-2-sulfonic acid octadec-9-enyl-amide (N15) is a novel PPAR alpha/gamma dual agonist synthesized in our laboratory. The present study investigates the efficacy and safety of N15 on insulin resistance regulation in high fat diet (HFD)-and streptozotocin (STZ)-induced diabetic mice and in palmitic acid (PA)-induced HepG2 cells. Our results showed that N15 remarkably ameliorated insulin resistance and dyslipidemia in vivo, as well as rectified the glucose consumption and gluconeogenesis in vitro. Moreover, the glucose-lowering effect of N15 was associated with PPAR gamma mediated up-regulation of hepatic glucose consumption and down-regulation of gluconeogenesis. Meanwhile, N15 exerted advantageous effects on glucose and lipid metabolism without triggering weight gain and hepatotoxicity in mice. In conclusion, our data demonstrated that by alleviating glucose and lipid abnormalities, N15 could be used as a potential prophylactic and therapeutic agent against type 2 diabetes and related metabolic disorders.