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

Khaled I. Alatibi,Judith Hagenbuchner,Ute Spiekerkoetter,Jerry Vockley,Michael J. Ausserlechner,Sarah C. Grünert,Zeinab Wehbe,Sara Tucci,Daniela Karall

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.

Highlights

Long-chain fatty acid oxidation disorders are inherited metabolic diseases affecting the degradation of chain fatty acids with a chain length >C12
Long-Chain Fatty Acid Oxidation Disorders Result in Different Alteration of the Previous reports have shown that fibroblasts from very long-chain acyl-CoA dehydrogenase (VLCAD)-/- mice have–/
Mice have an altered lipidome [12]. To investigate whether this effect occurs in fibroblasts from patients lipidome [12]

Summary

Introduction

Long-chain fatty acid oxidation disorders (lc-FAOD) are inherited metabolic diseases affecting the degradation of chain fatty acids with a chain length >C12. Enabled a valuable and fast screening for lc-FAOD based on a specific acylcarnitine pattern for each disease [2,3] These metabolites result from impaired metabolism of lc-fatty acids in organs and tissues due to mitochondrial leakage or active transport of accumulating metabolites by the carnitine shuttle towards the cytosol, and can be measured in DBS [4]. This same technology allows newborn screening for these autosomal recessive diseases, and accumulated data from many newborn screening programs worldwide identify a total incidence for fatty acid oxidation disorder of about 1:9.300 newborns [5]. Treatment of lc-FAOD includes avoidance of fasting as well as a fat-restricted and fat-modified diet in which lc-dietary fatty acids are replaced in part by medium-chain fatty acids (MCT oil) [6,7]

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Discussion

Conclusion