PPARγ Modulates Long Chain Fatty Acid Processing in the Intestinal Epithelium

Nuclear receptor PPAR gamma affects lipid metabolism in several tissues, but its role in intestinal lipid metabolism has not been explored. As alterations have been observed in the plasma lipid profile of ad libitum fed intestinal epithelium-specific PPAR gamma knockout mice (iePPAR gamma KO), we submitted these mice to lipid gavage challenges. Within hours after gavage with long chain unsaturated fatty acid (FA)-rich canola oil, the iePPAR gamma KO mice had higher plasma free FA levels and lower gastric inhibitory polypeptide levels than their wild-type (WT) littermates, and altered expression of incretin genes and lipid metabolism-associated genes in the intestinal epithelium. Gavage with the medium chain saturated FA-rich coconut oil did not result in differences between the two genotypes. Furthermore, the iePPAR gamma KO mice did not exhibit defective lipid uptake and stomach emptying; however, their intestinal transit was more rapid than in WT mice. When fed a canola oil-rich diet for 4.5 months, iePPAR gamma KO mice had higher body lean mass than the WT mice. We conclude that intestinal epithelium PPAR gamma is activated preferentially by long chain unsaturated FAs compared to medium chain saturated FAs. Furthermore, we hypothesize that the iePPAR gamma KO phenotype originates from altered lipid metabolism and release in epithelial cells, as well as changes in intestinal motility.