ReviewThis article belongs to the Special Issue Lipid Metabolism in Pathology and Health.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.This research was funded by FCT/MEC (PIDDAC) for their financial support to LAQVREQUIMTE (UIDB/50006/2020), CESAM (UIDP/50017/2020 + UIDB/50017/2020 + LA/P/0094/2020),
and the RNEM-Portuguese Mass Spectrometry Network (LISBOA-01-0145-FEDER-402-022125), financed
by FCT/MCTES through national funds and, where applicable, co-financed by the FEDER, within
the PT2020 Partnership Agreement and Compete 2020. Ana Moreira thanks the research contract
under the research unit LAQV-REQUIMTE. Inês M. S. Guerra (2021.04754.BD) and Helena B. Ferreira
(2020.04611.BD) are grateful to FCT for the PhD grants. Tânia Melo thanks the Junior Researcher contract
in the scope of the Individual Call to Scientific Employment Stimulus 2020 (CEECIND/01578/2020). The
authors are thankful to the COST Action EpiLipidNET, CA19105-Pan-European Network in Lipidomics,
and EpiLipidomics.info:eu-repo/semantics/publishedVersio
