Sorting out the functional role(s) of peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta) in cell proliferation and cancer

Abstract

Peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta) has many beneficial physiological functions ranging from enhancing fatty acid catabolism, improving insulin sensitivity, inhibiting inflammation and increasing oxidative myofibers allowing for improved athletic performance. Thus, given the potential for targeting PPARbeta/delta for the prevention and/or treatment of diseases including diabetes, dyslipidemias, metabolic syndrome and cancer, it is critical to clarify the functional role of PPARbeta/delta in cell proliferation and associated disorders such as cancer. However, there is considerable controversy whether PPARbeta/delta stimulates or inhibits cell proliferation. This review summarizes the literature describing the influence of PPARbeta/delta on cell proliferation, with an emphasis toward dissecting the data that give rise to opposing hypotheses. Suggestions are offered to standardize measurements associated with these studies so that interlaboratory comparisons can be accurately assessed.

Fig. 1

Chemical structure of ligands for PPARβ/δ.

Fig. 2

Modulation of gene expression by PPARβ/δ. (A) Transcriptional up-regulation of direct PPARβ/δ target genes. (B) Epigenetic regulation of gene expression by PPARβ/δ. PPARβ/δ can interfere with other transcription factors by physical interactions and inhibit expression of these gene products. This type of inhibition has been demonstrated for a number of inflammatory signaling cascades, including NF-κB, STAT3, BCL6 and AP1. (C) Transcriptional repression