Department of General Pediatrics, Adolescent Medicine and Neonatology, Faculty of Medicine, Medical Centre-University of Freiburg, 79106 Freiburg, Germany.
Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany.
Cells. 2021 May 18;10(5):1239. doi: 10.3390/cells10051239.
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.
长链脂肪酸氧化障碍（lc-FAOD）是一组影响长链脂肪酸降解的疾病。为了研究细胞脂质组的疾病特异性改变，我们对肉碱棕榈酰基转移酶 II、极长链酰基辅酶 A 脱氢酶和长链 3-羟基酰基辅酶 A 脱氢酶患者的成纤维细胞进行了非定向脂质组学分析。我们证明了线粒体心磷脂的深度重塑。异常的磷脂酰胆碱/磷脂酰乙醇胺比值以及血小板质和溶血磷脂的含量增加支持了 lc-FAOD 中炎症表型的理论。此外，我们描述了 LCHAD 缺乏症中鞘磷脂/神经酰胺和鞘磷脂/己糖神经酰胺比值增加，这可能有助于 LCHADD/三功能蛋白缺乏症的神经病变表型。
