Lipidomic and Proteomic Alterations Induced by Even and Odd Medium-Chain Fatty Acids on Fibroblasts of Long-Chain Fatty Acid Oxidation Disorders.
Acyl-CoA Dehydrogenase, Long-Chain
/ deficiency
Caprylates
/ pharmacology
Cardiolipins
/ metabolism
Cell Line
Female
Fibroblasts
/ drug effects
Genotype
Heptanoates
/ pharmacology
Humans
Lipid Metabolism, Inborn Errors
/ genetics
Lipidomics
/ methods
Male
Mitochondria
/ drug effects
Phosphatidylcholines
/ metabolism
Phosphatidylethanolamines
/ metabolism
Proteome
/ metabolism
Proteomics
/ methods
Sphingolipids
/ metabolism
lipidomics
long-chain fatty acid oxidation disorders
medium-chain fatty acids
protein homeostasis
proteomics
sphingolipid biosynthesis flux
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
29 Sep 2021
29 Sep 2021
Historique:
received:
02
08
2021
revised:
17
09
2021
accepted:
22
09
2021
entrez:
13
10
2021
pubmed:
14
10
2021
medline:
3
11
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34638902
pii: ijms221910556
doi: 10.3390/ijms221910556
pmc: PMC8508682
pii:
doi:
Substances chimiques
Caprylates
0
Cardiolipins
0
Heptanoates
0
Phosphatidylcholines
0
Phosphatidylethanolamines
0
Proteome
0
Sphingolipids
0
phosphatidylethanolamine
39382-08-6
Acyl-CoA Dehydrogenase, Long-Chain
EC 1.3.8.8
octanoic acid
OBL58JN025
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Deutsche Forschungsgemeinschaft
ID : TU492/3-1
Organisme : Ultragenyx Pharmaceutical
ID : ST-2019
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