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
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Research Support, Non-U.S. Gov't
MeSH terms
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Acyl-CoA Dehydrogenase, Long-Chain / deficiency
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Acyl-CoA Dehydrogenase, Long-Chain / genetics
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Cardiolipins / metabolism
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Carnitine O-Palmitoyltransferase / deficiency
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Carnitine O-Palmitoyltransferase / genetics
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Case-Control Studies
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Cells, Cultured
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Ceramides / metabolism
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Fatty Acids / metabolism*
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Female
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Fibroblasts / enzymology*
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Humans
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Lipid Metabolism, Inborn Errors / enzymology*
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Lipid Metabolism, Inborn Errors / genetics
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Lipidomics*
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Long-Chain-3-Hydroxyacyl-CoA Dehydrogenase / deficiency
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Long-Chain-3-Hydroxyacyl-CoA Dehydrogenase / genetics
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Male
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Metabolism, Inborn Errors / enzymology
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Metabolism, Inborn Errors / genetics
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Metabolome*
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Oxidation-Reduction
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Skin / enzymology*
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Sphingolipids / metabolism
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Tandem Mass Spectrometry
Substances
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Cardiolipins
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Ceramides
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Fatty Acids
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Sphingolipids
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Long-Chain-3-Hydroxyacyl-CoA Dehydrogenase
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Acyl-CoA Dehydrogenase, Long-Chain
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Carnitine O-Palmitoyltransferase
Supplementary concepts
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Carnitine palmitoyl transferase 2 deficiency