ROLE OF DIETARY SPHINGOLIPIDS AND INHIBITORS OF SPHINGOLIPID METABOLISM IN CANCER AND OTHER DISEASES

Sphingolipids are found in all eukaryotic and some prokaryotic organis ms and participate in the regulation of cell growth, differentiation, and diverse cell functions including cell-cell communication, cell-sub stratum interactions and intracellular signal transduction. Nonetheles s, the field of nutrition has given scant attention to these compounds so that little is known about the following fundamental questions: Wh at is the fate of sphingolipids that are consumed in food? Does consum ption of dietary sphingolipids affect the behavior of cells in the gas trointestinal tract or other organs? How do other factors in the diet affect sphingolipid metabolism? Several recent findings underscore the importance of these questions, for examples: 1) Sphingolipids are dig ested throughout the GI tract to ceramide and sphingosine, which are h ighly bioactive compounds that affect cellular regulatory pathways; 2) addition of sphingomyelin to a standard AIN diet (which is essentiall y devoid of sphingolipids) reduces the appearance of aberrant colonic crypts, and perhaps the number of tumors, in mice treated with a colon carcinogen; and 3) an enzyme of sphingolipid metabolism has been disc overed to be the target of a class of toxic and carcinogenic mycotoxin s called fumonisins. Given these recent findings, it is possible that some of the confusion that has arisen regarding the relationships betw een dietary fat and disease might be due to the lack of consideration of the sphingolipids that are also present.