S04: Understanding the changes evoked by chronic peroxisome proliferators-activated receptor (PPAR) agonism

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor of ligand-activated transcription factors involved in regulating glucose and lipid metabolism. The PPAR subfamily consists of three members; PPARbeta/delta, PPARalpha, and PPARgamma. PPAR agonists from single subtype to multiple subtype or partial agonists have being developed for the treatment of type 2 diabetes, dyslipidemia and obesity. Even though PPAR agonists are not genotoxic, carcinogenicity studies in rodents with PPAR gamma and dual PPAR gamma/alpha agonists have found various tumours, especially mesenchymal sarcomas in rats, mice, and hamsters, and rat urinary bladder urothelial tumours (El-Hage, 2005). These mesenchymal sarcomas appear to be preferential to the subcutaneous adipose tissue rather than the visceral adipose tissue beds; however the mode of action for the development of these tumours has not been elucidated. To develop our understanding of why PPAR agonists have differences in tumour risk between adipose depots; we expanded our knowledge of the physiological and functional differences between these adipose depots, with a particular focus on factors that can impact and influence tumourigenesis, through the use of transcriptomics.