Lipidomic and Proteomic Alterations Induced by Even and Odd Medium-Chain Fatty Acids on Fibroblasts of Long-Chain Fatty Acid Oxidation Disorders |
| |
Authors: | Khaled I. Alatibi,Stefan Tholen,Zeinab Wehbe,Judith Hagenbuchner,Daniela Karall,Michael J. Ausserlechner,Oliver Schilling,Sarah C. Grü nert,Jerry Vockley,Sara Tucci |
| |
Abstract: | Medium-chain fatty acids (mc-FAs) are currently applied in the treatment of long-chain fatty acid oxidation disorders (lc-FAOD) characterized by impaired β-oxidation. Here, we performed lipidomic and proteomic analysis in fibroblasts from patients with very long-chain acyl-CoA dehydrogenase (VLCADD) and long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHADD) deficiencies after incubation with heptanoate (C7) and octanoate (C8). Defects of β-oxidation induced striking proteomic alterations, whereas the effect of treatment with mc-FAs was minor. However, mc-FAs induced a remodeling of complex lipids. Especially C7 appeared to act protectively by restoring sphingolipid biosynthesis flux and improving the observed dysregulation of protein homeostasis in LCHADD under control conditions. |
| |
Keywords: | lipidomics proteomics medium-chain fatty acids long-chain fatty acid oxidation disorders protein homeostasis sphingolipid biosynthesis flux |
|
|