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Uptake and Metabolism of Sphingolipids in Isolated Intestinal Loops of Mice^1,2,3,

Department of Biochemistry ^* Department of Pathology and Division of Animal Resources, Emory University School of Medicine, Atlanta, GA 30322-3050

Sphingolipids are found in all eukaryotic organisms. However, little is known about the digestion, uptake and subsequent metabolism of these constituents of food. In this study, radiolabeled sphingolipids were placed in isolated intestinal segments of female CF1 mice, and the metabolism and distribution of the radiolabel were followed. Most of the sphingomyelin was degraded to ceramide and other products in all regions of the intestine, and increasing amounts of several [³H]-labeled sphingolipids appeared in the tissues. Small amounts of the radiolabel disappeared from the intestinal loops and appeared in liver within the first 30 to 60 min implying that neither intact sphingomyelin nor its metabolites are transported very efficiently from the intestine to other organs. There were different degrees of uptake and metabolism of sphingomyelin, [4,5-³H-sphinganyl]ceramide, and [³H]sphingosine. The [³H]sphingomyelin was also administered by gavage and the appearance along the intestine measured. After 90 min, 12% was found in the cecum and colon. These results establish that some of the sphingomyelin that enters the gastrointestinal tract is hydrolyzed and taken up by the intestine, with the lipid backbone being degraded or reutilized for complex sphingolipid synthesis; however, at least a portion passes into the large intestine. The appearance of bioactive compounds throughout the gastrointestinal tract may alter the behavior of intestinal cells.

KEY WORDS: • sphingomyelin • ceramide • mice • sphingosine • intestinal uptake

¹ Portions of this study were presented at two of the Annual Meetings of the Federation of the American Societies for Experimental Biology [Burnham, F. S., Bowman, B. B., Young, W., Moorwessel, M. M. & Merrill, A. H., Jr. (1989) Sphingolipid uptake by isolated segments of the rat intestine. FASEB J. 3: A469 (abs.) and Dillehay, D. L., Crall, K. J., Webb, S. K., Schmelz, E. & Merrill, A. H., Jr. (1993) Dietary sphingomyelin inhibits 1,2-dimethylhydrazine-induced cancer in CF1 mice. FASEB J. 7: A398 (abs.)].

² Supported by funds from the National Dairy Board and administered in cooperation with the National Dairy Council.

³ The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact.

⁴ To whom correspondence and reprint requests should be addressed at: Department of Biochemistry, 4113 Rollins Research Center, Emory University, Atlanta, GA 30322-3050.

Manuscript received 23 July 1993. Revision accepted 17 December 1993.

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