ACTIVATORS OF THE NUCLEAR RECEPTOR PPAR-GAMMA ENHANCE COLON POLYP FORMATION

A high-fat diet increases the risk of colon, breast and prostate cance r. The molecular mechanism by which dietary lipids promote tumorigenes is is unknown. Their effects may be mediated at least in part by the p eroxisome proliferator-activated receptors (PPARs). These ligand-activ ated nuclear receptors modulate gene expression in response to fatty a cids, lipid-derived metabolites and antidiabetic drugs. To explore the role of the PPARs in diet-induced carcinogenesis, we treated mice pre disposed to intestinal neoplasia with a synthetic PPAR gamma ligand. R eflecting the pattern of expression of PPAR gamma in the gastrointesti nal tract, treated mice developed a considerably greater number of pol yps in the colon but not in the small intestine, indicating that PPAR gamma activation may provide a molecular link between a high-fat diet and increased risk of colorectal cancer.