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

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)...

Descripción completa

Detalles Bibliográficos
Autores principales: Alatibi, Khaled I., Tholen, Stefan, Wehbe, Zeinab, Hagenbuchner, Judith, Karall, Daniela, Ausserlechner, Michael J., Schilling, Oliver, Grünert, Sarah C., Vockley, Jerry, Tucci, Sara
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8508682/
https://www.ncbi.nlm.nih.gov/pubmed/34638902
http://dx.doi.org/10.3390/ijms221910556
_version_ 1784582155672748032
author Alatibi, Khaled I.
Tholen, Stefan
Wehbe, Zeinab
Hagenbuchner, Judith
Karall, Daniela
Ausserlechner, Michael J.
Schilling, Oliver
Grünert, Sarah C.
Vockley, Jerry
Tucci, Sara
author_facet Alatibi, Khaled I.
Tholen, Stefan
Wehbe, Zeinab
Hagenbuchner, Judith
Karall, Daniela
Ausserlechner, Michael J.
Schilling, Oliver
Grünert, Sarah C.
Vockley, Jerry
Tucci, Sara
author_sort Alatibi, Khaled I.
collection PubMed
description 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.
format Online
Article
Text
id pubmed-8508682
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-85086822021-10-13 Lipidomic and Proteomic Alterations Induced by Even and Odd Medium-Chain Fatty Acids on Fibroblasts of Long-Chain Fatty Acid Oxidation Disorders Alatibi, Khaled I. Tholen, Stefan Wehbe, Zeinab Hagenbuchner, Judith Karall, Daniela Ausserlechner, Michael J. Schilling, Oliver Grünert, Sarah C. Vockley, Jerry Tucci, Sara Int J Mol Sci Article 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. MDPI 2021-09-29 /pmc/articles/PMC8508682/ /pubmed/34638902 http://dx.doi.org/10.3390/ijms221910556 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Alatibi, Khaled I.
Tholen, Stefan
Wehbe, Zeinab
Hagenbuchner, Judith
Karall, Daniela
Ausserlechner, Michael J.
Schilling, Oliver
Grünert, Sarah C.
Vockley, Jerry
Tucci, Sara
Lipidomic and Proteomic Alterations Induced by Even and Odd Medium-Chain Fatty Acids on Fibroblasts of Long-Chain Fatty Acid Oxidation Disorders
title Lipidomic and Proteomic Alterations Induced by Even and Odd Medium-Chain Fatty Acids on Fibroblasts of Long-Chain Fatty Acid Oxidation Disorders
title_full Lipidomic and Proteomic Alterations Induced by Even and Odd Medium-Chain Fatty Acids on Fibroblasts of Long-Chain Fatty Acid Oxidation Disorders
title_fullStr Lipidomic and Proteomic Alterations Induced by Even and Odd Medium-Chain Fatty Acids on Fibroblasts of Long-Chain Fatty Acid Oxidation Disorders
title_full_unstemmed Lipidomic and Proteomic Alterations Induced by Even and Odd Medium-Chain Fatty Acids on Fibroblasts of Long-Chain Fatty Acid Oxidation Disorders
title_short Lipidomic and Proteomic Alterations Induced by Even and Odd Medium-Chain Fatty Acids on Fibroblasts of Long-Chain Fatty Acid Oxidation Disorders
title_sort lipidomic and proteomic alterations induced by even and odd medium-chain fatty acids on fibroblasts of long-chain fatty acid oxidation disorders
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8508682/
https://www.ncbi.nlm.nih.gov/pubmed/34638902
http://dx.doi.org/10.3390/ijms221910556
work_keys_str_mv AT alatibikhaledi lipidomicandproteomicalterationsinducedbyevenandoddmediumchainfattyacidsonfibroblastsoflongchainfattyacidoxidationdisorders
AT tholenstefan lipidomicandproteomicalterationsinducedbyevenandoddmediumchainfattyacidsonfibroblastsoflongchainfattyacidoxidationdisorders
AT wehbezeinab lipidomicandproteomicalterationsinducedbyevenandoddmediumchainfattyacidsonfibroblastsoflongchainfattyacidoxidationdisorders
AT hagenbuchnerjudith lipidomicandproteomicalterationsinducedbyevenandoddmediumchainfattyacidsonfibroblastsoflongchainfattyacidoxidationdisorders
AT karalldaniela lipidomicandproteomicalterationsinducedbyevenandoddmediumchainfattyacidsonfibroblastsoflongchainfattyacidoxidationdisorders
AT ausserlechnermichaelj lipidomicandproteomicalterationsinducedbyevenandoddmediumchainfattyacidsonfibroblastsoflongchainfattyacidoxidationdisorders
AT schillingoliver lipidomicandproteomicalterationsinducedbyevenandoddmediumchainfattyacidsonfibroblastsoflongchainfattyacidoxidationdisorders
AT grunertsarahc lipidomicandproteomicalterationsinducedbyevenandoddmediumchainfattyacidsonfibroblastsoflongchainfattyacidoxidationdisorders
AT vockleyjerry lipidomicandproteomicalterationsinducedbyevenandoddmediumchainfattyacidsonfibroblastsoflongchainfattyacidoxidationdisorders
AT tuccisara lipidomicandproteomicalterationsinducedbyevenandoddmediumchainfattyacidsonfibroblastsoflongchainfattyacidoxidationdisorders

Ejemplares similares