Role of peroxisome-proliferator-activated receptor beta/delta (PPARbeta/delta) in gastrointestinal tract function and disease.

PPARbeta/delta (peroxisome-proliferator-activated receptor beta/delta) is one of three PPARs in the nuclear hormone receptor superfamily that are collectively involved in the control of lipid homoeostasis among other functions. PPARbeta/delta not only acts as a ligand-activated transcription factor, but also affects signal transduction by interacting with other transcription factors such as NF-kappaB (nuclear factor kappaB). Constitutive expression of PPARbeta/delta in the gastrointestinal tract is very high compared with other tissues and its potential physiological roles in this tissue include homoeostatic regulation of intestinal cell proliferation/differentiation and modulation of inflammation associated with inflammatory bowel disease and colon cancer. Analysis of mouse epithelial cells in the intestine and colon has clearly demonstrated that ligand activation of PPARbeta/delta induces terminal differentiation. The PPARbeta/delta target genes mediating this effect are currently unknown. Emerging evidence suggests that PPARbeta/delta can suppress inflammatory bowel disease through PPARbeta/delta-dependent and ligand-independent down-regulation of inflammatory signalling. However, the role of PPARbeta/delta in colon carcinogenesis remains controversial, as conflicting evidence suggests that ligand activation of PPARbeta/delta can either potentiate or attenuate this disease. In the present review, we summarize the role of PPARbeta/delta in gastrointestinal physiology and disease with an emphasis on findings in experimental models using both high-affinity ligands and null-mouse models.