Applications of metabolomics for understanding the action of peroxisome proliferator-activated receptors (PPARs) in diabetes, obesity and cancer

Zsuzsanna Ament, Mojgan Masoodi, Julian L Griffin

The peroxisome proliferator-activated receptors (PPARs) are a set of three nuclear hormone receptors that together play a key role in regulating metabolism, particularly the switch between the fed and fasted state and the metabolic pathways involving fatty-acid oxidation and lipid metabolism. In addition, they have a number of important developmental and regulatory roles outside metabolism. The PPARs are also potent targets for treating type II diabetes, dyslipidemia and obesity, although a number of individual agonists have also been linked to unwanted side effects, and there is a complex relationship between the PPARs and the development of cancer. This review examines the part that metabolomics, including lipidomics, has played in elucidating the roles PPARs have in regulating systemic metabolism, as well as their role in aspects of drug-induced cancer and xenobiotic metabolism. These studies have defined the role PPARδ plays in regulating fatty-acid oxidation in adipose tissue and the interaction between aging and PPARα in the liver. The potential translational benefits of these approaches include widening the role of PPAR agonists and improved monitoring of drug efficacy.