Lipidome plasticity in medium- and long-chain fatty acid oxidation disorders: Insights from dried blood spot lipidomics

IF 3.9 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Molecular and cell biology of lipids Pub Date : 2025-05-01 DOI:10.1016/j.bbalip.2025.159621

Inês M.S. Guerra , Hugo Rocha , Sónia Moreira , Ana Gaspar , Ana C. Ferreira , Helena Santos , Esmeralda Rodrigues , Paulo Castro-Chaves , Tânia Melo , Laura Goracci , Pedro Domingues , Ana S.P. Moreira , M. Rosário Domingues

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引用次数: 0

Abstract

Fatty acid (FA) oxidation disorders (FAOD) are characterized by accumulation of specific acylcarnitines (CAR) and FA and can lead to potentially severe complications. In this study, dried blood spots (DBS) combined with LC-MS lipidomics analysis were used to assess lipidome plasticity in medium-chain acyl-CoA dehydrogenase deficiency (MCADD), long-chain hydroxyacyl-CoA dehydrogenase deficiency (LCHADD), and very long-chain acyl-CoA dehydrogenase deficiency (VLCADD), compared to control (CT) individuals, for screening potential prognostic biomarkers.

Statistically significant variations were found in CAR, biomarkers for FAOD diagnosis, but other lipid species showed variations depending on the FAOD. Common changes in all FAOD included a few phosphatidylcholine (PC) lipid species, notably an up-regulation of LPC 16:1, possibly associated with a higher risk of cardiovascular disease (CVD). In LCHADD and VLCADD, an up-regulation of odd-chain PC (PC 33:0, PC 35:4 and PC 37:4) was observed. VLCADD exhibited higher levels of odd-chain TG, while LCHADD showed an up-regulation of ceramide (Cer 41:2;O2). The increase in the Cer class has been found to be associated with neurodegeneration and may contribute to the risk of developing this condition in LCHADD. An upregulation of ether-linked PC lipid species, including plasmenyl (known as endogenous antioxidants), was observed in MCADD, possibly as a response to increased oxidative stress reported in this disorder.

Overall, DBS combined with lipidomics effectively pinpoints the lipid plasticity in FAOD, highlighting potential specific biomarkers for disease prognosis that warrant further validation for their association with the development of FAOD comorbidities.

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中长链脂肪酸氧化紊乱中的脂质体可塑性：来自干血斑脂质组学的见解

脂肪酸（FA）氧化障碍（FAOD）的特征是特异性酰基肉碱（CAR）和FA的积累，并可能导致潜在的严重并发症。在本研究中，采用干血斑（DBS）结合LC-MS脂质组学分析来评估中链酰基辅酶a脱氢酶缺乏症（MCADD）、长链羟基酰基辅酶a脱氢酶缺乏症（LCHADD）和极长链酰基辅酶a脱氢酶缺乏症（VLCADD）与对照组（CT）相比的脂质组可塑性，以筛选潜在的预后生物标志物。在CAR （FAOD诊断的生物标志物）中发现了统计学上显著的差异，但其他脂质种类根据FAOD表现出差异。所有FAOD的共同变化包括一些磷脂酰胆碱（PC）脂质种类，特别是LPC 16:1的上调，可能与心血管疾病（CVD）的高风险相关。在LCHADD和VLCADD中，奇链PC上调（pc33:0， pc35:4和pc37:4）。VLCADD表现出更高的奇链TG水平，而LCHADD则表现出神经酰胺的上调（Cer 41:2;O2）。Cer类别的增加已被发现与神经退行性变有关，并可能增加LCHADD患者发生这种情况的风险。在MCADD中观察到包括plasmenyl（内源性抗氧化剂）在内的醚连接PC脂质的上调，可能是对这种疾病中氧化应激增加的反应。总体而言，DBS联合脂质组学有效地确定了FAOD的脂质可塑性，突出了疾病预后的潜在特异性生物标志物，这些生物标志物与FAOD合并症的发展相关，值得进一步验证。

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来源期刊

Biochimica et biophysica acta. Molecular and cell biology of lipids 生物-生化与分子生物学

CiteScore

11.00

自引率

2.10%

发文量

109

审稿时长

53 days

期刊介绍： BBA Molecular and Cell Biology of Lipids publishes papers on original research dealing with novel aspects of molecular genetics related to the lipidome, the biosynthesis of lipids, the role of lipids in cells and whole organisms, the regulation of lipid metabolism and function, and lipidomics in all organisms. Manuscripts should significantly advance the understanding of the molecular mechanisms underlying biological processes in which lipids are involved. Papers detailing novel methodology must report significant biochemical, molecular, or functional insight in the area of lipids.