Selective Absorption of Dietary Sphingoid Bases from the Intestine via Efflux by P-Glycoprotein in Rats.

Various physiological functions of dietary sphingolipids, such as preventing inflammation and improving the skin barrier function, have been recently demonstrated. The sphingolipid most commonly used as a foodstuff is glucosylceramide from plant sources, which is composed of sphingoid bases that are distinctive from those found in mammals. Although the structure of sphingoid bases in higher plants is more complicated than the structure of those in mammals, the fate of dietary sphingolipids of plant origin is still not understood. In the present study, we investigated the absorption of 4,8-sphingadienine that originated from maize glucosylceramide in the rat intestine by using a lipid absorption assay of lymph collected from the thoracic duct. The cumulative recovery of 4,8-sphingadienine in the lymph was lower than that of sphingosine. Verapamil, a P-glycoprotein inhibitor, significantly increased the absorption of 4,8-sphingadienine but did not affect the absorption of sphingosine. Plant-derived sphingoid bases were detected in the ceramide fraction of lymph fluid by using liquid chromatography-mass spectrometry analysis. These results indicate that 4,8-sphingadienine that originates from the glucosylceramide of higher plants is poorly absorbed in the intestine because of efflux by P-glycoprotein and can be incorporated into a ceramide moiety, at least in part, in intestinal endothelial cells.

Dietary sphingolipids improve skin barrier functions via the upregulation of ceramide synthases in the epidermis.

Sphingolipids are ubiquitous in eukaryotic organisms and are significant components in foods. It has been reported that treatment with sphingolipids prevents colon cancer, improves skin barrier function and suppresses inflammatory responses. However, the mechanisms for those effects of dietary sphingolipids are not well understood. In this study, to investigate the effects of dietary glucosylceramide (GluCer) and sphingomyelin (SM) on skin function, we characterized the recovery of skin barrier function and the change in sphingolipid metabolism-related enzymes in the epidermis using a special Mg-deficient diet-induced atopic dermatitis-like skin and tape-stripping damaged skin murine models. Our results show that dietary GluCer and SM accelerate the recoveries of damaged skin barrier functions. Correspondingly, dietary sphingolipids significantly upregulated the expression of ceramide synthases 3 and 4 in the epidermis of the atopic dermatitis-like skin model (P < 0.05). In the case of cultured cells, the expression of ceramide synthases 2-4 in normal human foreskin keratinocytes was significantly upregulated by treatment with 0.001-0.1 µm sphingoid bases (sphinganine, sphingosine and trans-4,cis-8-sphingadienine) (P < 0.05). These results suggest that the effects of dietary sphingolipids might be due to the activation of ceramide synthesis in the skin, rather than the direct reutilization of dietary sphingolipids. Our findings provide a novel insight into the mechanisms of the skin barrier improving effect and a more comprehensive understanding of dietary sphingolipids.