Four-dimensional lipidomics profiling in X-linked adrenoleukodystrophy using trapped ion mobility mass spectrometry.

Autor:	Jaspers YRJ; Laboratory Genetic Metabolic Diseases, Department of Laboratory Medicine, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands; Amsterdam Gastroenterology Endocrinology Metabolism Institute, Amsterdam, The Netherlands; Amsterdam Neuroscience institute, Amsterdam, The Netherlands., Meyer SW; Bruker Daltonics GmbH & Co. KG, Bremen, Germany., Pras-Raves ML; Laboratory Genetic Metabolic Diseases, Department of Laboratory Medicine, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands; Bioinformatics Laboratory, Department of Epidemiology and Data Science, Amsterdam Public Health Research Institute, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands; Core Facility Metabolomics, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands., Dijkstra IME; Laboratory Genetic Metabolic Diseases, Department of Laboratory Medicine, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands., Wever EJM; Laboratory Genetic Metabolic Diseases, Department of Laboratory Medicine, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands; Bioinformatics Laboratory, Department of Epidemiology and Data Science, Amsterdam Public Health Research Institute, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands; Core Facility Metabolomics, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands., Dane AD; Laboratory Genetic Metabolic Diseases, Department of Laboratory Medicine, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands; Bioinformatics Laboratory, Department of Epidemiology and Data Science, Amsterdam Public Health Research Institute, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands; Core Facility Metabolomics, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands., van Klinken JB; Laboratory Genetic Metabolic Diseases, Department of Laboratory Medicine, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands; Bioinformatics Laboratory, Department of Epidemiology and Data Science, Amsterdam Public Health Research Institute, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands; Core Facility Metabolomics, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands., Salomons GS; Laboratory Genetic Metabolic Diseases, Department of Laboratory Medicine, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands; Core Facility Metabolomics, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands; Department of Pediatrics, Emma Children's Hospital, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands., Houtkooper RH; Laboratory Genetic Metabolic Diseases, Department of Laboratory Medicine, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands; Amsterdam Gastroenterology Endocrinology Metabolism Institute, Amsterdam, The Netherlands; Emma Center for Personalized Medicine, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands., Engelen M; Amsterdam Neuroscience institute, Amsterdam, The Netherlands; Department of Pediatric Neurology, Amsterdam Leukodystrophy Center, Emma Children's Hospital, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands., Kemp S; Laboratory Genetic Metabolic Diseases, Department of Laboratory Medicine, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands; Amsterdam Gastroenterology Endocrinology Metabolism Institute, Amsterdam, The Netherlands; Amsterdam Neuroscience institute, Amsterdam, The Netherlands. Electronic address: s.kemp@amsterdamumc.nl., Van Weeghel M; Laboratory Genetic Metabolic Diseases, Department of Laboratory Medicine, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands; Amsterdam Gastroenterology Endocrinology Metabolism Institute, Amsterdam, The Netherlands; Core Facility Metabolomics, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands., Vaz FM; Laboratory Genetic Metabolic Diseases, Department of Laboratory Medicine, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands; Amsterdam Gastroenterology Endocrinology Metabolism Institute, Amsterdam, The Netherlands; Core Facility Metabolomics, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands.
Jazyk:	angličtina
Zdroj:	Journal of lipid research [J Lipid Res] 2024 Jun; Vol. 65 (6), pp. 100567. Date of Electronic Publication: 2024 May 23.
DOI:	10.1016/j.jlr.2024.100567
Abstrakt:	Lipids play pivotal roles in an extensive range of metabolic and physiological processes. In recent years, the convergence of trapped ion mobility spectrometry and MS has enabled 4D-lipidomics, a highly promising technology for comprehensive lipid analysis. 4D-lipidomics assesses lipid annotations across four distinct dimensions-retention time, collisional cross section, m/z (mass-to-charge ratio), and MS/MS spectra-providing a heightened level of confidence in lipid annotation. These advantages prove particularly valuable when investigating complex disorders involving lipid metabolism, such as adrenoleukodystrophy (ALD). ALD is characterized by the accumulation of very-long-chain fatty acids (VLCFAs) due to pathogenic variants in the ABCD1 gene. A comprehensive 4D-lipidomics strategy of ALD fibroblasts demonstrated significant elevations of various lipids from multiple classes. This indicates that the changes observed in ALD are not confined to a single lipid class and likely impacts a broad spectrum of lipid-mediated physiological processes. Our findings highlight the incorporation of mainly saturated and monounsaturated VLCFA variants into a range of lipid classes, encompassing phosphatidylcholines, triacylglycerols, and cholesterol esters. These include ultra-long-chain fatty acids with a length of up to thirty carbon atoms. Lipid species containing C26:0 and C26:1 were the most frequently detected VLCFA lipids in our study. Furthermore, we report a panel of 121 new candidate biomarkers in fibroblasts, exhibiting significant differentiation between controls and individuals with ALD. In summary, this study demonstrates the capabilities of a 4D-lipid profiling workflow in unraveling novel insights into the intricate lipid modifications associated with metabolic disorders like ALD. Competing Interests: Conflict of interest Sven W. Meyer is employed at Bruker Daltonics GmbH. All the other authors declarethat they have no conflict of interest with the contents of this article. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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