Abstract 115: Microsomal Triglyceride Transfer Protein Is a Major Determinant of Plasma Ceramide And Sphingomyelin but Not of Hexosylceramide and Lactosylceramide
Sphingolipids are present in cell membranes and in plasma lipoproteins. Mechanisms of sphingolipid transport to plasma lipoproteins are unknown. We found that plasma levels of ceramide and sphingomyelin were significantly lower in homozygous abetalipoproteinemia subjects defective in microsomal triglyceride transfer protein (MTP) function compared with heterozygotes, and in mice deficient in both intestinal and hepatic MTP compared with control mice. In contrast, plasma concentrations of hexosylceramide, lactosylceramide and different sphingosines were not affected by MTP deficiency. MTP deficiency had no effect on ceramide and sphingomyelin synthesis, but reduced their secretion. MTP was found to transfer ceramide and sphingomyelin. These studies suggest that MTP is a critical determinant of plasma ceramide and sphingomyelins, but not of glycosylceramide and sphingosine. The MTP-dependent transport processes to carry ceramide and sphingomyelin might have evolved to protect against toxicity associated with cellular ceramide accretions and to supply sphingomyelin to other tissues to maintain membrane integrity and to control cellular differentiation and proliferation.
Author Disclosures: J. Iqbal: None. M.T. Walsh: None. S.M. Hammad: None. M. Cuchel: None. P. Tarugi: None. R.A. Hegele: None. N.O. Davidson: None. D.J. Rader: None. R.L. Klein: None. M. Hussain: None.
- © 2015 by American Heart Association, Inc.