Ceramide Is Metabolized to Acylceramide and Stored in Lipid Droplets

Can E. Senkal, Mohamed F. Salama, Ashley J. Snider, Janet J. Allopenna, Nadia A. Rana, Antonius Koller, Yusuf A. Hannun, Lina M. Obeid

Research output: Contribution to journalArticlepeer-review

102 Scopus citations

Abstract

In an approach aimed at defining interacting partners of ceramide synthases (CerSs), we found that fatty acyl-CoA synthase ACSL5 interacts with all CerSs. We demonstrate that ACSL5-generated FA-CoA was utilized with de novo ceramide for the generation of acylceramides, poorly studied ceramide metabolites. Functionally, inhibition of ceramide channeling to acylceramide enhanced accumulation of de novo ceramide and resulted in augmentation of ceramide-mediated apoptosis. Mechanistically, we show that acylceramide generation is catalyzed by diacylglycerol acyltransferase 2 (DGAT2) on lipid droplets. In summary, this study identifies a metabolic pathway of acylceramide generation and its sequestration in LDs in cells and in livers of mice on a high-fat diet. The study also implicates this pathway in ceramide-mediated apoptosis, and has implications in co-regulation of triglyceride and sphingolipid metabolisms.

Original languageEnglish (US)
Pages (from-to)686-697
Number of pages12
JournalCell Metabolism
Volume25
Issue number3
DOIs
StatePublished - Mar 7 2017
Externally publishedYes

Keywords

  • acylceramide
  • apoptosis
  • ceramide
  • ceramide synthase
  • CerS
  • DGAT
  • diacylglycerol acyltransferase
  • fatty acyl-CoA synthase
  • lipid droplets
  • sphingolipids

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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