M1731 Sphingosine-1-Phosphate Regulates Barrier Function in Cultured Intestinal Epithelial Cells and Murine Intestinal Tissue

Abstract

assessed by stable isotope methodology after administration of U-13C-glucose and 1-13Clactose. Concentrations of the EFA linoleic acid (LA), and the enzyme activity and mRNA expression of lactase, were measured in the mucosa of proximal, mid and distal small intestine. Results: Mice fed the EFA-deficient diet were markedly EFA-deficient (triene/ tetraene ratio 0.23±0.06 vs. 0.01±0.00 in controls, p<0.05) with a profound lower fat absorption of dietary fat (81±3 vs. 99±0% in controls, of ingested amount, p<0.05). EFA deficiency did not affect the histology or proliferative capacity of the small intestine as demonstrated by the histological and proliferative staining, and by the morphometrcal measurements of the small intestinal villi. Blood C6-glucose appearance and disappearance were similar in both groups, indicating unaffected monosaccharide absorption. In contrast, blood appearance of 13C-glucose, originating from 13C-lactose, was delayed in EFA-deficient mice. EFA deficiency profoundly reduced lactase activity (-58%, p<0.01) and mRNA expression (-55%, p<0.01) in mid small intestine. Both lactase activity and its mRNA expression strongly correlated with mucosal LA concentrations (r=0.89 and 0.79, resp., p< 0.01). Conclusions: EFA deficiency in mice inhibits the capacity to digest lactose, but does not affect small intestinal histology. These data underscore the observation that EFA deficiency functionally impairs the small intestine, possibly mediated by low LA levels in the enterocytes. This research was funded by the Dutch Digestive Foundation (MWO 04-38).