CERAMIDE IS METABOLIZED TO ACYLCERAMIDE AND STORED IN LIPID DROPLETS
| Autor: | Nadia A. Rana, Lina M. Obeid, Mohamed Salama, Antonius Koller, Janet Allopenna, Ashley J. Snider, Can E. Senkal, Yusuf A. Hannun |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Ceramide Physiology Acylation ACSL5 Ceramides Diet High-Fat Article Substrate Specificity 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Protein Domains Lipid droplet Coenzyme A Ligases Animals Humans Diacylglycerol O-Acyltransferase Gene Silencing Molecular Biology Ceramide synthase biology Cell Biology Lipid signaling Feeding Behavior Lipid Droplets HCT116 Cells Sphingolipid Mice Inbred C57BL Metabolic pathway 030104 developmental biology chemistry Biochemistry Liver 030220 oncology & carcinogenesis Fatty-acyl-CoA synthase biology.protein lipids (amino acids peptides and proteins) Oxidoreductases |
| Popis: | In an approach aimed at defining interacting partners of ceramide synthases (CerS), we found that fatty acyl CoA synthase ACSL5 interacts with all CerS. 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 LD in cells and in livers of mice on a high fat diet. The study also implicates this novel pathway in ceramide-mediated apoptosis, and has implications in co-regulation of triglyceride and sphingolipid metabolisms. |
| Databáze: | OpenAIRE |
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