Harnessing the benefits of PPARβ/δ agonists

Lipid mediators have complex effects on the cell; one of the key transcriptional factors that moderate prolifera- 20tion and inflammatory effects is PPARβ/δ. Following highly successful clinical trials using the PPARβ/δ agonists 21GW501516 for treatment of diabetes, GSK announced that any further research would be discontinued due to 22preclinical trials in rodentswhich linked this drug towide spread tumour development. In this reviewwe outline 23the dualmolecular functions of PPARβ/δ and connect these to the diverse results fromin vitro studies, and draw 24parallelswith the outcomes of animal and human studies. The PPARβ/δ agonists have a great potential in terms of 25therapy, andwe hope to provide some insight into the reasonswhy such contrasting results have been published. 26The discussion presented here is important to the future development of PPARβ/δ agonists for the clinic, and for a 27fuller understanding for their complex regulatory roles in the cell