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

Table 1 PPAR agonists and their treatment of type II diabetes and obesity

Drug class	Target	Mode of action	Examples	Concerns
Fibrates	PPARα	Target cholesterol metabolism Increase fatty acid oxidation	Clofibrate, gemfibrozil, ciprofibrate, bezafibrate, fenofibrate	Increased risk of cancer (especially liver)
Thiazolidinediones	PPARγ	Insulin resistance is decreased, adipocyte differentiation is increased, leptin decreased and adiponectin increased	Rosiglitazone (Avandia^®) pioglitazone (Actos^®) troglitazone (Rezulin^®)	Rosiglitazone - concern over cardiovascular events; pioglitazone - concerns over bladder cancer; troglitazone withdrawn due to increased drug-induced hepatitis
PPAR-delta agonists	PPARδ	Stimulate fatty acid oxidation in skeletal muscle and adipose tissue, decrease insulin resistance, stimulate glucose metabolism	None currently on the market	They have been linked with increased and decreased risks of cancer; drug-induced myopathy
Dual agonists and PPARpan^a agonists	Two or all three receptors	A combination of the effects of the pure agonists	Aleglitazar, muraglitazar and tesaglitazar	Increased risk of certain cancers; increased risk of myocardial infarction

This table shows some of the different types of drugs that are used to treat type II diabetes and obesity by targeting at least one of the PPAR receptors. Given the wide range of drugs that fall into this class of compounds, the list is not comprehensive but used to illustrate the diverse range of drugs available. ^aA PPARpan drug targets all three PPAR receptors.

ISSN: 1756-994X