scholarly journals Docosahexaenoic Acid Attenuates Mitochondrial Alterations and Oxidative Stress Leading to Cell Death Induced by Very Long-Chain Fatty Acids in a Mouse Oligodendrocyte Model

2020 ◽  
Vol 21 (2) ◽  
pp. 641 ◽  
Author(s):  
Thomas Nury ◽  
Margaux Doria ◽  
Gérard Lizard ◽  
Anne Vejux
Keyword(s):  
Oxidative Stress ◽  
Fatty Acids ◽  
Docosahexaenoic Acid ◽  
Membrane Integrity ◽  
Long Chain Fatty Acids ◽  
Western Blot Assay ◽  
Cytotoxic Effects ◽  
The Impact ◽  
Long Chain ◽  
Chain Fatty Acids

In the case of neurodegenerative pathologies, the therapeutic arsenal available is often directed towards the consequences of the disease. The purpose of this study is, therefore, to evaluate the ability of docosahexaenoic acid (DHA), a molecule present in certain foods and considered to have health benefits, to inhibit the cytotoxic effects of very long-chain fatty acids (C24:0, C26:0), which can contribute to the development of some neurodegenerative diseases. The effect of DHA (50 µM) on very long-chain fatty acid-induced toxicity was studied by several complementary methods: phase contrast microscopy to evaluate cell viability and morphology, the MTT test to monitor the impact on mitochondrial function, propidium iodide staining to study plasma membrane integrity, and DHE staining to measure oxidative stress. A Western blot assay was used to assess autophagy through modification of LC3 protein. The various experiments were carried out on the cellular model of 158N murine oligodendrocytes. In 158N cells, our data establish that DHA is able to inhibit all tested cytotoxic effects induced by very long-chain fatty acids.

Long chain fatty acids can form aggregates and affect the membrane integrity

2021 ◽  
Vol 204 ◽  
pp. 111795
Author(s):  
Gulen Melike Demirbolat ◽  
Goknil Pelin Coskun ◽  
Omer Erdogan ◽  
Ozge Cevik
Keyword(s):  
Fatty Acids ◽  
Membrane Integrity ◽  
Long Chain Fatty Acids ◽  
Long Chain ◽  
Chain Fatty Acids

59  Late gestation supplementation of long chain fatty acids increases foal docosahexaenoic acid concentrations at birth

2021 ◽  
Vol 100 ◽  
pp. 103522
Author(s):  
E. Snyder ◽  
N. Shost ◽  
R. Miller ◽  
K. Fikes ◽  
R. Smith ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Docosahexaenoic Acid ◽  
Long Chain Fatty Acids ◽  
Long Chain ◽  
Chain Fatty Acids

scholarly journals Lipid remodeling and an altered membrane-associated proteome may drive the differential effects of EPA and DHA treatment on skeletal muscle glucose uptake and protein accretion

2018 ◽  
Vol 314 (6) ◽  
pp. E605-E619 ◽  
Author(s):  
Stewart Jeromson ◽  
Ivor Mackenzie ◽  
Mary K. Doherty ◽  
Phillip D. Whitfield ◽  
Gordon Bell ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Glucose Uptake ◽  
Long Chain Fatty Acids ◽  
Differential Effects ◽  
Epa And Dha ◽  
Metabolic Remodeling ◽  
The Impact ◽  
Long Chain ◽  
Chain Fatty Acids

In striated muscle, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have differential effects on the metabolism of glucose and differential effects on the metabolism of protein. We have shown that, despite similar incorporation, treatment of C2C12 myotubes (CM) with EPA but not DHA improves glucose uptake and protein accretion. We hypothesized that these differential effects of EPA and DHA may be due to divergent shifts in lipidomic profiles leading to altered proteomic profiles. We therefore carried out an assessment of the impact of treating CM with EPA and DHA on lipidomic and proteomic profiles. Fatty acid methyl esters (FAME) analysis revealed that both EPA and DHA led to similar but substantials changes in fatty acid profiles with the exception of arachidonic acid, which was decreased only by DHA, and docosapentanoic acid (DPA), which was increased only by EPA treatment. Global lipidomic analysis showed that EPA and DHA induced large alterations in the cellular lipid profiles and in particular, the phospholipid classes. Subsequent targeted analysis confirmed that the most differentially regulated species were phosphatidylcholines and phosphatidylethanolamines containing long-chain fatty acids with five (EPA treatment) or six (DHA treatment) double bonds. As these are typically membrane-associated lipid species we hypothesized that these treatments differentially altered the membrane-associated proteome. Stable isotope labeling by amino acids in cell culture (SILAC)-based proteomics of the membrane fraction revealed significant divergence in the effects of EPA and DHA on the membrane-associated proteome. We conclude that the EPA-specific increase in polyunsaturated long-chain fatty acids in the phospholipid fraction is associated with an altered membrane-associated proteome and these may be critical events in the metabolic remodeling induced by EPA treatment.

The Impact of a Ketogenic Diet and Liver Dysfunction on Serum Very Long-Chain Fatty Acids Levels

Lipids ◽  
2013 ◽  
Vol 48 (4) ◽  
pp. 405-409 ◽  
Author(s):  
T. J. Stradomska ◽  
M. Bachański ◽  
J. Pawłowska ◽  
M. Syczewska ◽  
A. Stolarczyk ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Ketogenic Diet ◽  
Liver Dysfunction ◽  
Long Chain Fatty Acids ◽  
The Impact ◽  
Long Chain ◽  
Chain Fatty Acids

Supranormal Electroretinogram inFat-1Mice with Retinas Enriched in Docosahexaenoic Acid and n-3 Very Long Chain Fatty Acids (C24–C36)

2009 ◽  
Vol 50 (9) ◽  
pp. 4394 ◽  
Author(s):  
Miyoung Suh ◽  
Yves Sauve´ ◽  
Krystal J. Merrells ◽  
Jing X. Kang ◽  
David W. L. Ma
Keyword(s):  
Fatty Acids ◽  
Docosahexaenoic Acid ◽  
Long Chain Fatty Acids ◽  
Long Chain ◽  
Chain Fatty Acids

Metabolomics of Lean/Overweight Insulin-Resistant Females Reveals Alterations in Steroids and Fatty Acids

2020 ◽  
Author(s):  
Ilhame Diboun ◽  
Layla Al-Mansoori ◽  
Hend Al-Jaber ◽  
Omar Albagha ◽  
Mohamed A Elrayess
Keyword(s):  
Fatty Acids ◽  
Roc Analysis ◽  
Linear Models ◽  
Partial Least Square ◽  
Least Square ◽  
Long Chain Fatty Acids ◽  
Cross Sectional ◽  
The Impact ◽  
Long Chain ◽  
Chain Fatty Acids

Abstract Background The global diabetes epidemic is largely attributed to obesity-triggered metabolic syndrome. However, the impact of insulin resistance (IR) prior to obesity on the high prevalence of diabetes and the molecular mediators remain largely unknown. This study aims to compare the metabolic profiling of apparently healthy lean/overweight participants with IR and insulin sensitivity (IS), and identify the metabolic pathways underlying IR. Methods In this cross-sectional study, clinical and metabolic data for 200 seemingly healthy young female participants (100 IR and 100 IS) was collected from Qatar Biobank. Orthogonal partial least square analysis was performed to assess the extent of separation between individuals from the 2 groups based on measured metabolites. Classical linear models were used to identify the metabolic signature of IR, followed by elastic-net-regularized generalized linear model (GLMNET) and receiver operating characteristic (ROC) analysis to determine top metabolites associated with IR. Results Compared to lean/overweight participants with IS, those with IR showed increased androgenic steroids, including androsterone glucuronide, in addition to various microbiota byproducts, such as the phenylalanine derivative carboxyethylphenylalanine. On the other hand, participants with IS had elevated levels of long-chain fatty acids. A ROC analysis suggested better discriminatory performance using 20 metabolites selected by GLMNET in comparison to the classical clinical traits (area under curve: 0.93 vs 0.73, respectively). Conclusion Our data confirm the multifactorial mechanism of IR with a diverse spectrum of emerging potential biomarkers, including steroids, long-chain fatty acids, and microbiota metabolites. Further studies are warranted to validate these markers for diagnostic and therapeutic applications.

scholarly journals Induction of Mitochondrial Changes Associated with Oxidative Stress on Very Long Chain Fatty Acids (C22:0, C24:0, or C26:0)-Treated Human Neuronal Cells (SK-NB-E)

2012 ◽  
Vol 2012 ◽  
pp. 1-15 ◽  
Author(s):  
Amira Zarrouk ◽  
Anne Vejux ◽  
Thomas Nury ◽  
Hammam I. El Hajj ◽  
Madouda Haddad ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Fatty Acids ◽  
Cell Counting ◽  
Long Chain Fatty Acids ◽  
Superoxide Anion Production ◽  
Mitochondrial Dysfunctions ◽  
Whole Cells ◽  
Potential Risk Factors ◽  
Long Chain ◽  
Chain Fatty Acids

In Alzheimer's disease, lipid alterations point towards peroxisomal dysfunctions. Indeed, a cortical accumulation of saturated very long chain fatty acids (VLCFAs: C22:0, C24:0, C26:0), substrates for peroxisomalβ-oxidation, has been found in Alzheimer patients. This study was realized to investigate the effects of VLCFAs at the mitochondrial level since mitochondrial dysfunctions play crucial roles in neurodegeneration. On human neuronal SK-NB-E cells treated with C22:0, C24:0, or C26:0 (0.1–20 μM; 48 h), an inhibition of cell growth and mitochondrial dysfunctions were observed by cell counting with trypan blue, MTT assay, and measurement of mitochondrial transmembrane potential (Δψm) with DiOC6(3). A stimulation of oxidative stress was observed with DHE and MitoSOX used to quantify superoxide anion production on whole cells and at the mitochondrial level, respectively. With C24:0 and C26:0, by Western blotting, lower levels of mitochondrial complexes III and IV were detected. After staining with MitoTracker and by transmission electron microscopy used to study mitochondrial topography, mass and morphology, major changes were detected in VLCFAs treated-cells: modification of the cytoplasmic distribution of mitochondria, presence of large mitochondria, enhancement of the mitochondrial mass. Thus, VLCFAs can be potential risk factors contributing to neurodegeneration by inducing neuronal damages via mitochondrial dysfunctions.

scholarly journals N-Acetylcysteine Reverses the Mitochondrial Dysfunction Induced by Very Long-Chain Fatty Acids in Murine Oligodendrocyte Model of Adrenoleukodystrophy

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1826
Author(s):  
Jie Zhou ◽  
Marcia R. Terluk ◽  
Paul J. Orchard ◽  
James C. Cloyd ◽  
Reena V. Kartha
Keyword(s):  
Oxidative Stress ◽  
Fatty Acids ◽  
Cell Death ◽  
Membrane Potential ◽  
Mitochondrial Dysfunction ◽  
Long Chain Fatty Acids ◽  
Specific Effects ◽  
Low Concentrations ◽  
Long Chain ◽  
Chain Fatty Acids

The accumulation of saturated very long-chain fatty acids (VLCFA, ≥C22:0) due to peroxisomal impairment leads to oxidative stress and neurodegeneration in X-linked adrenoleukodystrophy (ALD). Among the neural supporting cells, myelin-producing oligodendrocytes are the most sensitive to the detrimental effect of VLCFA. Here, we characterized the mitochondrial dysfunction and cell death induced by VLFCA, and examined whether N-acetylcysteine (NAC), an antioxidant, prevents the cytotoxicity. We exposed murine oligodendrocytes (158 N) to hexacosanoic acid (C26:0, 1–100 µM) for 24 h and measured reactive oxygen species (ROS) and cell death. Low concentrations of C26:0 (≤25 µM) induced a mild effect on cell survival with no alterations in ROS or total glutathione (GSH) concentrations. However, analysis of the mitochondrial status of cells treated with C26:0 (25 µM) revealed depletion in mitochondrial GSH (mtGSH) and a decrease in the inner membrane potential. These results indicate that VLCFA disturbs the mitochondrial membrane potential causing ROS accumulation, oxidative stress, and cell death. We further tested whether NAC (500 µM) can prevent the mitochondria-specific effects of VLCFA in C26:0-treated oligodendrocytes. Our results demonstrate that NAC improves mtGSH levels and mitochondrial function in oligodendrocytes, indicating that it has potential use in the treatment of ALD and related disorders.

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