Abstract：
Fatty acid oxidation disorders (FAODs) are inborn errors of metabolism (IEMs) caused by defects in the fatty acid (FA) mitochondrial β-oxidation. The most common FAODs are characterized by the accumulation of medium-chain FAs and long-chain (3-hydroxy) FAs (and their carnitine derivatives), respectively. These deregulations are associated with lipotoxicity which affects several organs and potentially leads to life-threatening complications and comorbidities. Changes in the lipidome have been associated with several diseases, including some IEMs. In FAODs, the alteration of acylcarnitines (CARs) and FA profiles have been reported in patients and animal models, but changes in polar and neutral lipid profile are still scarcely studied. In this review, we present the main findings on FA and CAR profile changes associated with FAOD pathogenesis, their correlation with oxidative damage, and the consequent disturbance of mitochondrial homeostasis. Moreover, alterations in polar and neutral lipid classes and lipid species identified so far and their possible role in FAODs are discussed. We highlight the need of mass-spectrometry-based lipidomic studies to understand (epi)lipidome remodelling in FAODs, thus allowing to elucidate the pathophysiology and the identification of possible biomarkers for disease prognosis and an evaluation of therapeutic efficacy.
摘要：
脂肪酸氧化障碍（FAOD）是由脂肪酸（FA）线粒体β氧化缺陷引起的先天性代谢错误（IEM）。最常见的FAOD的特征是中链FAs和长链（3-羟基）FAs（及其肉碱衍生物）的积累，分别。这些放松与影响多个器官的脂毒性相关,并可能导致危及生命的并发症和合并症。脂质组的变化与几种疾病有关，包括一些IEM。在FAOD中，已经在患者和动物模型中报道了酰基肉碱（CAR）和FA谱的改变，但是极性和中性脂质分布的变化仍然很少研究。在这次审查中,我们提出了与FAOD发病机制相关的FA和CAR谱变化的主要发现，它们与氧化损伤的相关性，以及随之而来的线粒体稳态紊乱。此外，到目前为止，已确定的极性和中性脂质类别以及脂质种类的变化及其在FAOD中的可能作用进行了讨论。我们强调了基于质谱的脂质组学研究的必要性，以了解FAOD中的（epi）脂质重组，因此，允许阐明病理生理学和鉴定可能的生物标志物的疾病预后和治疗效果的评估。
