Different Lipid Signature in Fibroblasts of Long-Chain Fatty Acid Oxidation Disorders

Cells. 2021 May 18;10(5):1239. doi: 10.3390/cells10051239.

Abstract

Long-chain fatty acid oxidation disorders (lc-FAOD) are a group of diseases affecting the degradation of long-chain fatty acids. In order to investigate the disease specific alterations of the cellular lipidome, we performed undirected lipidomics in fibroblasts from patients with carnitine palmitoyltransferase II, very long-chain acyl-CoA dehydrogenase, and long-chain 3-hydroxyacyl-CoA dehydrogenase. We demonstrate a deep remodeling of mitochondrial cardiolipins. The aberrant phosphatidylcholine/phosphatidylethanolamine ratio and the increased content of plasmalogens and of lysophospholipids support the theory of an inflammatory phenotype in lc-FAOD. Moreover, we describe increased ratios of sphingomyelin/ceramide and sphingomyelin/hexosylceramide in LCHAD deficiency which may contribute to the neuropathic phenotype of LCHADD/mitochondrial trifunctional protein deficiency.

Keywords: cardiolipine; ceramides; fatty acid oxidation disorders; lipidomic profiling; sphingomyelins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyl-CoA Dehydrogenase, Long-Chain / deficiency
  • Acyl-CoA Dehydrogenase, Long-Chain / genetics
  • Cardiolipins / metabolism
  • Carnitine O-Palmitoyltransferase / deficiency
  • Carnitine O-Palmitoyltransferase / genetics
  • Case-Control Studies
  • Cells, Cultured
  • Ceramides / metabolism
  • Fatty Acids / metabolism*
  • Female
  • Fibroblasts / enzymology*
  • Humans
  • Lipid Metabolism, Inborn Errors / enzymology*
  • Lipid Metabolism, Inborn Errors / genetics
  • Lipidomics*
  • Long-Chain-3-Hydroxyacyl-CoA Dehydrogenase / deficiency
  • Long-Chain-3-Hydroxyacyl-CoA Dehydrogenase / genetics
  • Male
  • Metabolism, Inborn Errors / enzymology
  • Metabolism, Inborn Errors / genetics
  • Metabolome*
  • Oxidation-Reduction
  • Skin / enzymology*
  • Sphingolipids / metabolism
  • Tandem Mass Spectrometry

Substances

  • Cardiolipins
  • Ceramides
  • Fatty Acids
  • Sphingolipids
  • Long-Chain-3-Hydroxyacyl-CoA Dehydrogenase
  • Acyl-CoA Dehydrogenase, Long-Chain
  • Carnitine O-Palmitoyltransferase

Supplementary concepts

  • Carnitine palmitoyl transferase 2 deficiency