Different Lipid Signature in Fibroblasts of Long-Chain Fatty Acid Oxidation Disorders
Khaled I. Alatibi,
Judith Hagenbuchner,
Zeinab Wehbe,
Daniela Karall,
Michael J. Ausserlechner,
Jerry Vockley,
Ute Spiekerkoetter,
Sarah C. Grünert,
Sara Tucci
Affiliations
Khaled I. Alatibi
Department of General Pediatrics, Adolescent Medicine and Neonatology, Faculty of Medicine, Medical Centre-University of Freiburg, 79106 Freiburg, Germany
Judith Hagenbuchner
Department of Pediatrics II, Medical University Innsbruck, 6020 Innsbruck, Austria
Zeinab Wehbe
Department of General Pediatrics, Adolescent Medicine and Neonatology, Faculty of Medicine, Medical Centre-University of Freiburg, 79106 Freiburg, Germany
Daniela Karall
Department of Pediatrics I, Medical University Innsbruck, 6020 Innsbruck, Austria
Michael J. Ausserlechner
Department of Pediatrics I, Medical University Innsbruck, 6020 Innsbruck, Austria
Jerry Vockley
School of Medicine, University of Pittsburgh, Pittsburgh, PA 15260, USA
Ute Spiekerkoetter
Department of General Pediatrics, Adolescent Medicine and Neonatology, Faculty of Medicine, Medical Centre-University of Freiburg, 79106 Freiburg, Germany
Sarah C. Grünert
Department of General Pediatrics, Adolescent Medicine and Neonatology, Faculty of Medicine, Medical Centre-University of Freiburg, 79106 Freiburg, Germany
Sara Tucci
Department of General Pediatrics, Adolescent Medicine and Neonatology, Faculty of Medicine, Medical Centre-University of Freiburg, 79106 Freiburg, Germany
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.
