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)

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.

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Long-chain fatty acids of peptococci and peptostreptococci

Journal of Clinical Microbiology ◽

10.1128/jcm.4.6.515-521.1976 ◽

1976 ◽

Vol 4 (6) ◽

pp. 515-521

Author(s):

C L Wells ◽

C R Field

Keyword(s):

Fatty Acids ◽

Fatty Acid ◽

Single Species ◽

Gas Liquid Chromatography ◽

Long Chain Fatty Acids ◽

Whole Cells ◽

Group I ◽

Group Ii ◽

Long Chain ◽

Chain Fatty Acids

The long-chain fatty acids extracted from the whole cells of 12 clinically significant species of peptococci and peptostreptococci were characterized by gas-liquid chromatography. The resulting methylated fatty acid profiles (and some unidentified compounds) of 82 strains allowed the 12 species to be separated into four groups. Fifteen strains of Peptostreptococcus anaerobius were placed in group I because they had a unique, prominent compound that occurred in the area where a C8 to C10 fatty acid would be expected. Group II, consisting of Peptostreptococcus intermedius, Peptostreptococcus micros, Peptostreptococcus parvulus, Peptococcus morbillorum, and Peptococcus constellatus, produced C14, C16:1, C18:1, and C18 fatty acids. Peptococcus prevotii, Peptococcus variabilus, Peptococcus magnus, Peptococcus asaccharolyticus, and Peptostreptococcus productus were placed in group III because they contained three to six additional, unidentified compounds that strikingly differentiated them from group II. Peptococcus saccharolyticus was the single species assigned to group IV because it yielded C14, C16, C18:1, C18, and C20 fatty acids and a prominent unidentified peak that occurred between C14 and C16 fatty acids. This study indicated that cellular long-chain fatty acids may be an important tool in clarifying the taxonomy of the peptococci and peptostreptococci.

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

Biomedicines ◽

10.3390/biomedicines9121826 ◽

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

International Journal of Molecular Sciences ◽

10.3390/ijms21020641 ◽

2020 ◽

Vol 21 (2) ◽

pp. 641 ◽

Cited By ~ 1

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.

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Diet supplemented with medium- and long-chain fatty acids does not affect lower GI motility and visceral pain in rats

10.26226/morressier.59a6b345d462b80290b5487f ◽

2017 ◽

Author(s):

Paula Mosinska

Keyword(s):

Fatty Acids ◽

Visceral Pain ◽

Long Chain Fatty Acids ◽

Long Chain ◽

Chain Fatty Acids ◽

Gi Motility

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Binding of bilirubin and long-chain fatty acids to human serum albumin with general remarks on displacement of firmly bound ligands

Scandinavian Journal of Clinical and Laboratory Investigation ◽

10.3109/00365517709091491 ◽

1977 ◽

Vol 37 (3) ◽

pp. 257-266 ◽

Cited By ~ 8

Author(s):

R. Brodersen ◽

L. Funding

Keyword(s):

Fatty Acids ◽

Human Serum Albumin ◽

Serum Albumin ◽

Human Serum ◽

Long Chain Fatty Acids ◽

Long Chain ◽

Chain Fatty Acids

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Differential Effects of Fatty Acid Saturation and Chain Length on NASH in Juvenile Iberian Pigs

Current Developments in Nutrition ◽

10.1093/cdn/nzaa050_005 ◽

2020 ◽

Vol 4 (Supplement_2) ◽

pp. 682-682 ◽

Cited By ~ 1

Author(s):

Kayla Dillard ◽

Morgan Coffin ◽

Gabriella Hernandez ◽

Victoria Smith ◽

Catherine Johnson ◽

...

Keyword(s):

Fatty Acids ◽

Body Weight ◽

Fatty Acid ◽

Liver Injury ◽

Olive Oil ◽

Coconut Oil ◽

Long Chain Fatty Acids ◽

Medium Chain ◽

Long Chain ◽

Chain Fatty Acids

Abstract Objectives Non-alcoholic fatty liver disease (NAFLD) represents the major cause of pediatric chronic liver pathology in the United States. The objective of this study was to compare the relative effect of inclusion of isocaloric amounts of saturated medium-chain fatty acids (hydrogenated coconut oil), saturated long-chain fatty acids (lard) and unsaturated long-chain fatty acids (olive oil) on endpoints of NAFLD and insulin resistance. Methods Thirty-eight 15-d-old Iberian pigs were fed 1 of 4 diets containing (g/kg body weight × d) 1) control (CON; n = 8): 0 g fructose, 10.5 g fat, and 187 kcal metabolizable energy (ME), 2) lard (LAR; n = 10): 21.6 g fructose, 17.1 g fat (100% lard) and 299 kcal ME, 3) hydrogenated coconut oil (COCO; n = 10): 21.6 g fructose, 16.9 g fat (42.5% lard and 57.5% coconut oil) and 299 kcal ME, and 4) olive oil (OLV, n = 10): 21.6 g fructose, 17.1 g fat (43.5% lard and 56.5% olive oil) and 299 kcal ME, for 9 consecutive weeks. Body weight was recorded every 3 d. Serum markers of liver injury and dyslipidemia were measured on d 60 at 2 h post feeding, with all other serum measures assessed on d 70. Liver tissue was collected on d 70 for histology, triacylglyceride (TG) quantification, and metabolomics analysis. Results Tissue histology indicated the presence of steatosis in LAR, COCO and OLV compared with CON (P ≤ 0.001), with a further increase in in non-alcoholic steatohepatitis (NASH) in OLV and COCO compared with LAR (P ≤ 0.01). Alanine and aspartate aminotransferases were higher in COCO and OLV (P ≤ 0.01) than CON. All treatment groups had lower liver concentrations of methyl donor's choline and betaine versus CON, while bile acids were differentially changed (P ≤ 0.05). COCO had higher levels of TGs with less carbons (Total carbons < 52) than all other groups (P ≤ 0.05). Several long-chain acylcarnitines involved in fat oxidation were higher in OLV versus all other groups (P ≤ 0.05). Conclusions Inclusion of fats enriched in medium-chain saturated and long-chain unsaturated fatty acids in a high-fructose high-fat diet increased liver injury, compared with fats with a long-chain saturated fatty acid profile. Further research is required to investigate the mechanisms causing this difference in physiological response to these dietary fat sources. Funding Sources ARI, AcornSeekers.

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