Lipidomic and Proteomic Alterations Induced by Even and Odd Medium-Chain Fatty Acids on Fibroblasts of Long-Chain Fatty Acid Oxidation Disorders

Khaled I. Alatibi; Stefan Tholen; Zeinab Wehbe; Judith Hagenbuchner; Daniela Karall; Michael J. Ausserlechner; Oliver Schilling; Sarah C. Grünert; Jerry Vockley; Sara Tucci

doi:10.3390/ijms221910556

International Journal of Molecular Sciences (Sep 2021)

Lipidomic and Proteomic Alterations Induced by Even and Odd Medium-Chain Fatty Acids on Fibroblasts of Long-Chain Fatty Acid Oxidation Disorders

Khaled I. Alatibi,
Stefan Tholen,
Zeinab Wehbe,
Judith Hagenbuchner,
Daniela Karall,
Michael J. Ausserlechner,
Oliver Schilling,
Sarah C. Grünert,
Jerry Vockley,
Sara Tucci

Affiliations

Khaled I. Alatibi: Department of General Pediatrics, Adolescent Medicine and Neonatology, Faculty of Medicine, Medical Centre-University of Freiburg, 79106 Freiburg, Germany
Stefan Tholen: Institute for Molecular Medicine and Cell Research, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany
Zeinab Wehbe: Department of Pediatric Hematology and Oncology, Center of Pediatric and Adolescent Medicine–Medical Center—University of Freiburg, Faculty of Medicine, 79106 Freiburg, Germany
Judith Hagenbuchner: Department of Pediatrics II, Medical University Innsbruck, 6020 Innsbruck, Austria
Daniela Karall: Department of Pediatrics I, Medical University Innsbruck, 6020 Innsbruck, Austria
Michael J. Ausserlechner: Department of Pediatrics I, Medical University Innsbruck, 6020 Innsbruck, Austria
Oliver Schilling: Institute for Molecular Medicine and Cell Research, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany
Sarah C. Grünert: Department of General Pediatrics, Adolescent Medicine and Neonatology, Faculty of Medicine, Medical Centre-University of Freiburg, 79106 Freiburg, Germany
Jerry Vockley: School of Medicine, University of Pittsburgh, Pittsburgh, PA 15260, USA
Sara Tucci: Department of General Pediatrics, Adolescent Medicine and Neonatology, Faculty of Medicine, Medical Centre-University of Freiburg, 79106 Freiburg, Germany

DOI: https://doi.org/10.3390/ijms221910556
Journal volume & issue: Vol. 22, no. 19
p. 10556

Abstract

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Medium-chain fatty acids (mc-FAs) are currently applied in the treatment of long-chain fatty acid oxidation disorders (lc-FAOD) characterized by impaired β-oxidation. Here, we performed lipidomic and proteomic analysis in fibroblasts from patients with very long-chain acyl-CoA dehydrogenase (VLCADD) and long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHADD) deficiencies after incubation with heptanoate (C7) and octanoate (C8). Defects of β-oxidation induced striking proteomic alterations, whereas the effect of treatment with mc-FAs was minor. However, mc-FAs induced a remodeling of complex lipids. Especially C7 appeared to act protectively by restoring sphingolipid biosynthesis flux and improving the observed dysregulation of protein homeostasis in LCHADD under control conditions.

Published in International Journal of Molecular Sciences

ISSN: 1661-6596 (Print); 1422-0067 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Biology (General); Science: Chemistry
Website: http://www.mdpi.com/journal/ijms

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