PPARγ physiology and pathology in gastrointestinal epithelial cells

Peroxisome proliferator-activated receptor-gamma (PPARγ) is expressed at very high levels in the gastrointestinal epithelium. Many of the functions of PPARγ in gastrointestinal epithelial cells have been elucidated in recent years, and a pattern is emerging which suggests that this receptor plays an important role in gastrointestinal physiology. There is also strong evidence that PPARγ is a colon cancer suppressor in pre-clinical rodent models of sporadic colon cancer, and there is considerable interest in exploitation of PPARγ agonists as prophylactic or chemopreventive agents in colon cancer. Studies in mice and in human colon cancer cell lines suggest several mechanisms that might account for the tumor suppressive effects of PPARγ agonists, although it is not in all cases clear whether these effects are altogether mediated by PPARγ. Conversely, several reports suggest that PPARγ agonists may promote colon cancer under certain circumstances. This possibility warrants considerable attention since several million individuals with type II diabetes are currently taking PPARγ agonists. This review will focus on recent data related to four critical questions: what is the physiological function of PPARγ in gastrointestinal epithelial cells; how does PPARγ suppress colon carcinogenesis; is PPARγ a tumor promoter; and what is the future of PPARγ in colon cancer prevention?