Polyunsaturated fatty acids reduce non-receptor-mediated transcellular permeation of protein across a model of intestinal epithelium in vitro

Background: Dietary polyunsaturated fatty acids influence the natural histo ry of intestinal inflammatory diseases. Varying the types of long-chain fat ty acids that are exposed to cells alters the physicochemical properties of cell membranes. This study aimed to determine whether such variations alte r transcellular and paracellular permeability in intestinal epithelium. Methods: Monolayers of Caco-2 cells, allowed to differentiate by culturing for 7 days following confluence, were used as the model for intestinal epit helium. Paracellular permeability was assessed by measurement of transepith elial resistance, while transcellular permeability was assessed by the tran sepithelial flux of horseradish peroxidase. Results: Exposure of the cells to 100 mu mol/L of palmitic acid, oleic acid , eicosapentaenoic acid, or linoleic acid, was not toxic to cells (measured by leakage of lactate dehydrogenase), and altered cell membrane fatty acid composition (as measured by gas chromatography). Flux of horseradish perox idase was significantly affected by 24 h fatty acid exposure (P = 0.038, AN OVA), being decreased by 23 +/- 6% (mean +/- SEM) by eicosapentaenoic acid and 25 +/- 3% by linoleic acid. Oleic acid, palmitic acid and butyrate, had no effect. Transepithelial resistance also varied significantly across the treatment groups (P < 0.001) due to a 28 +/- 5% increase induced by butyra te. The long-chain fatty acids had no effect. Conclusions: Both omega-3 and omega-6 polyunsaturated fatty acids reduce tr anscellular, non-receptor-mediated permeation of proteins across differenti ated Caco2 cell monolayers, without altering paracellular permeability. Alt eration of intestinal barrier function should be considered as a possible m echanism of action of dietary polyunsaturated fatty acids. (C) 2000 Blackwe ll Science Asia Pty Ltd.