Myristic Acid Remodels Sphingolipid Metabolism via Dual Pathways: Canonical d18-Sphingolipid Regulation and Non-Canonical d16-Sphingolipid Synthesis.

ABSTRACT: Background: Myristic acid (MA), a 14-carbon saturated fatty acid, serves as a precursor for the synthesis of non-canonical d16-sphingoid bases via its activated form, C14:0-CoA. However, its broader regulatory role in sphingolipid (SL) metabolism remains poorly defined. Methods: Using HepG2 cells treated with 50 μM MA, we found that sphingolipidomic analysis revealed reprogrammed sphingolipid metabolism. Results: In the canonical d18-SL pathway, MA directs its activated product C14:0-CoA into ceramide N-acyl chains and downstream metabolites-especially d18:1-C14:0 hexosylceramide. Concurrently, in the non-canonical d16-SL pathway, MA promotes d16-SL synthesis, especially d16:1-ceramides (Cer), d16:1-hexosylceramides (HexCer), and d16:1-C14:0 lactosylceramide. MA

SUBMITTER: You Y 

PROVIDER: S-EPMC12429915 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature