scholarly journals IDH1 Mutations Induce Organelle Defects Via Dysregulated Phospholipids

2020 ◽  
Author(s):  
Adrian Lita ◽  
Artem Pliss ◽  
Andrey Kuzmin ◽  
Tomohiro Yamasaki ◽  
Lumin Zhang ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Oleic Acid ◽  
Golgi Apparatus ◽  
Monounsaturated Fatty Acids ◽  
Idh1 Mutation ◽  
Structural Defects ◽  
Low Grade ◽  
List Type ◽  
Functional Link ◽  
Idh1 Mutations

SummaryCytosolic IDH1 enzyme plays a key, but currently unexplored, role in lipid biosynthesis. Using Raman imaging microscopy, we identified heterogeneous lipid profiles in cellular organelles attributed uniquely to IDH1 mutations. Via organelle lipidomics, we found an increase in saturated and monounsaturated fatty acids in the endoplasmic reticulum of IDH1mut cells compared with IDHWT glioma. We showed that these fatty acids incorporate into phospholipids and induce organelle dysfunctions, with prominent dilation of Golgi apparatus, which can be restored by transient knockdown of stearyl-CoA desaturase or inhibition of D-2-hydroxyglutarate (D-2HG) formation. We validated these findings using tissue from patients with glioma. Oleic acid addition led to increased sensitivity to apoptosis of IDH1mut cells compared with IDHWT. Addition of D-2HG to U251WT cells lead in increased ER and Golgi apparatus dilation. Collectively, these studies provide clinically relevant insights into the functional link between IDH1mut-induced lipid alterations and organelle dysfunction, with therapeutic implications.SignificanceGliomas are devastating tumors, with the most aggressive form—glioblastoma multiforme— correlated with a mean patient survival of 14.5 months. No curative treatment exists to date. Low-grade glioma (LGG) with the isocitrate dehydrogenase 1 (IDH1) mutation, R132H, provides a survival benefit to patients. Understanding the unique metabolic profile of IDH1mut could provide clues regarding its association with longer survival and information about therapeutic targets. Herein, we identified lipid imbalances in organelles, generated by IDHmut in cells and patient tissue, that were responsible for Golgi dilation and that correlated with increased survival. Addition of oleic acid, which tilted the balance towards elevated levels of monounsaturated fatty acids produced IDH1mut-specific cellular apoptosis.HighlightsSingle-organelle omics revealed unique alterations in lipid metabolism due to IDH1-mutations.IDH mutation leads to organelle-wide structural defects.IDH1 mutation leads to increased monounsaturated fatty acids levels in glioma cells and oligodendroglioma patient samples.Lipid alterations affect the membrane integrity of the Golgi apparatus.Increased D-2HG induced SCD expression and elevated monounsaturated fatty acidsTilting the balance toward more-abundant monounsaturated fatty acids leads to specific IDH1mut glioma apoptosis.

scholarly journals IDH1 Mutation in Gliomas in Mosul City - Iraq

2015 ◽  
Vol 3 (2) ◽  
pp. 250-255 ◽  
Author(s):  
Mohammed Sami Saeed
Keyword(s):  
Case Series ◽  
Idh1 Mutation ◽  
Teaching Hospitals ◽  
Low Grade ◽  
Isocitrate Dehydrogenase 1 ◽  
Secondary Glioblastoma ◽  
Idh1 R132h ◽  
Case Series Study ◽  
Idh1 Mutations ◽  
Prospective Case Series

BACKGROUND: IDH1 (isocitrate dehydrogenase 1) mutation might be encounter in the low grade glioma and directs the progression of the tumor to a higher grade.OBJECTIVE: To assess the frequency of IDH1 mutations in gliomas and to correlate the IDH1 positivity with the type and grade of tumors, the age and sex of the patients.MATERIAL AND METHODS: A retro– and prospective case series study. One hundred and nine cases of intracranial gliomas were collected between 2008 and 2014 from Mosul Private Laboratories and Al-Jamboree Teaching Hospitals in Mosul. IDH1 mutations were assessed immunohistochemically using anti-IDH1 R132H mouse monoclonal antibody.RESULTS: IDH1 mutation was perceived in 34.86% of gliomas. In adult gliomas, the secondary glioblastoma and the low-grade astrocytoma had the greatest values of IDH1 positivity (88.88% and 62.5% respectively), followed by oligoastrocytoma/oligodendroglioma (50.0%), and anaplastic astrocytoma (47.36%). The primary glioblastomsa showed 17.64% IDH1 positivity. Males and females expressed the IDH1 equally. While, there was no role of IDH1 in pediatric gliomas.CONCLUSION: IDH1 mutation is commonly present in adult gliomas particularly in low-grade gliomas, and secondary glioblastoma, with equal sex distribution, but it has no role in pediatric gliomas.

scholarly journals Fatty acid composition and sensory analysis in Boer kids meat

2014 ◽  
Vol 57 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Angela Cividini ◽  
Ana Kaić ◽  
Dragomir Kompan ◽  
Klemen Potočnik
Keyword(s):  
Fatty Acids ◽  
Fatty Acid Composition ◽  
Oleic Acid ◽  
Fatty Acid ◽  
Monounsaturated Fatty Acids ◽  
Longissimus Dorsi ◽  
Slaughter Weight ◽  
Weight Percentage ◽  
Acid Ratio ◽  
Slaughter Age

Abstract. This study was undertaken to characterize the fatty acid profile and sensory properties of longissimus dorsi (LD) muscle of Boer kids as affected by sex (17 male, 15 female) and slaughter weight (pre-weaned 20 kg, post-weaned 30 kg). Regarding sex differences, higher percentage amounts of lauric, myristic, pentadecanoic, linolenic and docosapentaenoic acids were found in LD muscle of male compared to female kids, whereas greater amounts of oleic acid were detected in LD muscle of female kids. Also, LD of male kids contained higher percentage amounts of saturated (SFA), polyunsaturated (PUFA) and n-3 polyunsaturated fatty acids (n-3 PUFA) while higher amounts of monounsaturated fatty acids (MUFA) were detected in LD of female kids. Regarding slaughter weight, percentage amounts of lauric, myristic, margaric, pentadecanoic, linolenic, linoleic, arachidonic and docosapentaenoic acids significantly decreased with age (P≤0.001), while percentage amounts of heptadecenoic and oleic acids significantly increased (P≤0.001). LD muscle from lighter kids contained higher percentage amounts of SFA and PUFA, while heavier kids had higher percentage amounts of MUFA and n-3/n-6 fatty acid ratio. Except meat colour, sensory traits (marbling, off-odour, flavour, juiciness and tenderness) were neither significantly affected by sex nor slaughter age.

scholarly journals IDH1 mutations induce organelle defects via dysregulated phospholipids

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Adrian Lita ◽  
Artem Pliss ◽  
Andrey Kuzmin ◽  
Tomohiro Yamasaki ◽  
Lumin Zhang ◽  
...  
Keyword(s):  
Oleic Acid ◽  
Tumor Biology ◽  
Monounsaturated Fatty Acids ◽  
Idh1 Mutation ◽  
Isocitrate Dehydrogenase 1 ◽  
Therapeutic Implications ◽  
Morphological Defects ◽  
Cellular Apoptosis ◽  
Organelle Morphology ◽  
Rate Limiting

AbstractInfiltrating gliomas are devastating and incurable tumors. Amongst all gliomas, those harboring a mutation in isocitrate dehydrogenase 1 mutation (IDH1mut) acquire a different tumor biology and clinical manifestation from those that are IDH1WT. Understanding the unique metabolic profile reprogrammed by IDH1 mutation has the potential to identify new molecular targets for glioma therapy. Herein, we uncover increased monounsaturated fatty acids (MUFA) and their phospholipids in endoplasmic reticulum (ER), generated by IDH1 mutation, that are responsible for Golgi and ER dilation. We demonstrate a direct link between the IDH1 mutation and this organelle morphology via D-2HG-induced stearyl-CoA desaturase (SCD) overexpression, the rate-limiting enzyme in MUFA biosynthesis. Inhibition of IDH1 mutation or SCD silencing restores ER and Golgi morphology, while D-2HG and oleic acid induces morphological defects in these organelles. Moreover, addition of oleic acid, which tilts the balance towards elevated levels of MUFA, produces IDH1mut-specific cellular apoptosis. Collectively, these results suggest that IDH1mut-induced SCD overexpression can rearrange the distribution of lipids in the organelles of glioma cells, providing new insight into the link between lipid metabolism and organelle morphology in these cells, with potential and unique therapeutic implications.

scholarly journals FATTY ACIDS COMPOSITION IN MACADAMIA SEDES OIL (MACADAMIA INTEGRIFOLIA) FROM ECUADOR

2017 ◽  
Vol 10 (2) ◽  
pp. 303 ◽  
Author(s):  
Wilman Carrillo ◽  
Cecilia Carpio ◽  
Dayana Morales ◽  
Edgardo Vilcacundo ◽  
Mario Alvarez
Keyword(s):  
Fatty Acids ◽  
Oleic Acid ◽  
Food Industry ◽  
Unsaturated Fatty Acids ◽  
Monounsaturated Fatty Acids ◽  
Fatty Acids Composition ◽  
Pressing Method ◽  
Mass Selective Detector ◽  
Macadamia Integrifolia ◽  
Selective Detector

Objective: The aim of this study was to determine the fatty acids composition in a macadamia seeds oil sample cultivated in Ecuador.Materials & Methods: macadamia oil was obtained of macadamia seeds using the cold pressing method. Fatty acids analysis was carried out using the Gas Chromathography method with a Mass Selective Detector (GC/MSD) and using the data base Library NIST14.L to identify the compounds.Results: macadamia seeds have a high content of unsaturated fatty acids with 41.36% of oleic acid. Macadamia seeds oil has 37.77% of polyunsaturated fatty acids of which 3.79% ɷ6 α- Linoleic and 33.98% of ɷ3 α- Linolenic. Macadamia seeds only have 9.33% of palmitic acid. Conclusions: Macadamia seeds are a good source of monounsaturated fatty acids oleic acid and with a good content of ɷ6 α- Linoleic and ɷ3 α- Linolenic. This profile enables their use as a good and healthy oil to be used in the food industry in Ecuador. Keywords: Macadamia, Macadamia integrifolia, Fatty acids, Gas chromatography-mass selective detector, Methyl ester, Omega acids.

scholarly journals Lipid accumulation and oxidation in glioblastoma multiforme

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Bouchra Taïb ◽  
Amine M. Aboussalah ◽  
Mohammed Moniruzzaman ◽  
Suming Chen ◽  
Norman J. Haughey ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Oleic Acid ◽  
Fatty Acid ◽  
Glioblastoma Multiforme ◽  
Lipid Droplets ◽  
Monounsaturated Fatty Acids ◽  
Acid Oxidation ◽  
Normal Brain ◽  
Lipid Species ◽  
Brain Tissues

AbstractGlioblastoma multiforme (GBM) is the most common and lethal primary malignant brain tumor in adults. Despite the multimodal standard treatments for GBM, the median survival is still about one year. Analysis of brain tissues from GBM patients shows that lipid droplets are highly enriched in tumor tissues while undetectable in normal brain tissues, yet the identity and functions of lipid species in GBM are not well understood. The aims of the present work are to determine how GBM utilizes fatty acids, and assess their roles in GBM proliferation. Treatment of U138 GBM cells with a monounsaturated fatty acid, oleic acid, induces accumulation of perilipin 2-coated lipid droplets containing triglycerides enriched in C18:1 fatty acid, and increases fatty acid oxidation. Interestingly, oleic acid also increases glucose utilization and proliferation of GBM cells. In contrast, pharmacologic inhibition of monoacylglycerol lipase attenuates GBM proliferation. Our findings demonstrate that monounsaturated fatty acids promote GBM proliferation via triglyceride metabolism, suggesting a novel lipid droplet-mediated pathway which may be targeted for GBM treatment.

scholarly journals Effects of Sowing Season on Agronomic Traits and Fatty Acid Metabolic Profiling in Three Brassica napus L. Cultivars

Metabolites ◽  
2019 ◽  
Vol 9 (2) ◽  
pp. 37 ◽  
Author(s):  
Xiaoyi Li ◽  
Lintao Wu ◽  
Guoliang Qiu ◽  
Tao Wang ◽  
Chunhong Liu ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Oleic Acid ◽  
Fatty Acid ◽  
Brassica Napus ◽  
Metabolic Profiling ◽  
Agronomic Traits ◽  
Saturated Fatty Acids ◽  
Fatty Acid Content ◽  
Monounsaturated Fatty Acids ◽  
Human Consumption

Decreasing saturated fatty acids and increasing monounsaturated fatty acids are desirable to improve oil for food. Seed oil content and fatty acid composition are affected by genotype and environment. Therefore, we systematically analyzed the agronomic traits and fatty acid metabolic profiling of Brassica napus (B. napus) seeds at different developmental stages in high level of oleic acid (HOA), medium level of oleic acid (MOA), and low level of oleic acid (LOA) B. napus cultivars, both sown in winter and summer. The results showed that all winter-sown cultivars produced 20% more seed yield than the summer-sown crop. The longer growing period of winter-sown B. napus resulted in higher biomass production. However, the fatty acid metabolism of individual cultivars was different between winter-sown rape (WAT) and summer-sown rape (SAT). The absolute fatty acid content of LOA and MOA cultivars in WAT were significantly higher than that in SAT, but that of HOA was opposite. Importantly, the levels of monounsaturated fatty acids (18:1; 20:1) in SAT were far more than those in WAT. These data indicate the quality of oil from the HOA in SAT is more suitable for human consumption than that in WAT.

scholarly journals FATTY ACID COMPOSITION OF THE FRUITS OF SYZYGIUM ZEYLANICUM (L.) DC. VAR. ZEYLANICUM

2017 ◽  
pp. 155-157
Author(s):  
Devi R. C. Bhanu ◽  
K. K. Sabu
Keyword(s):  
Fatty Acids ◽  
Fatty Acid Composition ◽  
Oleic Acid ◽  
Fatty Acid ◽  
Linoleic Acid ◽  
Acid Composition ◽  
Saturated Fatty Acids ◽  
Monounsaturated Fatty Acids ◽  
Nutritional Composition ◽  
Total Fatty Acids

Objective: Wild indigenous fruits are believed to be extremely nutritious, contributing a great deal to the general health of the tribal and rural population. To validate this claim, systematic studies are required to estimate their nutritional composition. The objective of the study was to analyze the fatty acid composition of Syzygium zeylanicum (L.) DC. var. zeylanicum.Methods: The fatty acid composition of S. zeylanicum var. zeylanicum fruits were analysed by GC-MS/MS.Results: The major fatty acids were cis-oleic acid (43.47±0.62 %) and linoleic acid (31.14±0.35%). Total monounsaturated fatty acids in the sample was 44.21%. Omega-6, omega-7 and omega-9 fatty acids were detected. The polyunsaturated fatty acids in thefruits were linoleic acid (31.14±0.35 %) and arachidonic acid (0.15±0.22 %), whereas 24.51 % of the total fatty acids were saturated. The ratio of unsaturated to saturated fatty acids was approximately 3:1. The order of abundance of fatty acids, in some of the healthiest oils, viz. olive, canola, peanut oils is, Oleic acid>Linoleic acid>Palmitic acid>Stearic acid and the same order was observed in the present study.Conclusion: Fruits of S. zeylanicum var. zeylanicum too shows a healthy balance between unsaturated and saturated fats. 

scholarly journals Physicochemical Properties and Fatty Acid Profile of African Elemi Fruit Pulp Oil Compared with Palm Kernel Oil

2020 ◽  
Vol 2 (6) ◽  
Author(s):  
D. B. Kiin-Kabari ◽  
P. S. Umunna ◽  
S. Y. Giami
Keyword(s):  
Fatty Acids ◽  
Oleic Acid ◽  
Fatty Acid ◽  
Stearic Acid ◽  
Palmitic Acid ◽  
Fatty Acid Profile ◽  
Palm Kernel ◽  
Monounsaturated Fatty Acids ◽  
Fruit Pulp ◽  
Kernel Oil

African elemi (Canarium schweinfurthii) fruit pulp oil was extracted and refined which yielded 39.5% oil. It was characterized for its physical, chemical, phytochemical properties and fatty acid profile in comparison with palm kernel oil (PKO). The result for physical properties revealed that there was no significant difference in the density, refractive index, and flash point of the oils. African elemi fruit pulp oil (AEO) had significantly (p>0.05) higher slip melting point and viscosity while significantly (p<0.05) lower smoke point and fire point. Chemical properties of the oils such as iodine, acid value, unsaponifiable matter and free fatty acids were significantly (p>0.05) higher in AEO with the values of 76.79 g/100 g, 0.94 mg KOH/g, 1.32 and 0.58%, respectively and significantly (p<0.05) lower in saponification and peroxide values, 155.47 mg KOH/g and 1.06 meq/kg, respectively compared to the values obtained for the PKO. Saturated fatty acid profile of AEO had the values of 9.44, 32.24 and 2.63% for myristic (C14:0), stearic acid (C18:0) and palmitic acid (C16:0) while PKO had the values of 48.00, 16.20, 2.50 and 8.40% for lauric (C12:0), myristic (C14:0), stearic acid (C18:0) and palmitic acid (C16:0), respectively. The monounsaturated fatty acids were oleic acid (C18:1) 30.24% for AEO and 15.0% for PKO making oleic acid the highest occurring monounsaturated fatty acids present in AEO. Thus, lauric acid (C12:0) and linoleic (C18:2) was not dictated in AEO while gadoleic (C20:1) was not dictated in PKO. Flavonoids, tannins, saponins, phytates and alkaloids had the values of 0.29, 0.33, 0.13, 0.13 and 0.74% for AEO and 0.32, 0.12, 0.24, 0.11 and 0.07% for PKO, respectively and all were within the acceptable limit of 3% for food products with respect to the phytochemical properties of the oils. The result for solid fat content - temperature profile revealed that PKO and AEO completely melted at 35 °C and 45 °C, respectively.

scholarly journals Oleic acid influences the adipogenesis of 3T3-L1 cells via DNA Methylation and may predispose to obesity and obesity-related disorders

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Malgorzata Malodobra-Mazur ◽  
Aneta Cierzniak ◽  
Tadeusz Dobosz
Keyword(s):  
Dna Methylation ◽  
Fatty Acids ◽  
Oleic Acid ◽  
Insulin Signaling ◽  
Stromal Cells ◽  
Glucose Utilization ◽  
Accumulation Rate ◽  
Monounsaturated Fatty Acids ◽  
Dna And Rna

Abstract Background Adipogenesis is the process of adipocytes formation from unspecialized progenitor cells called mesenchymal stromal cells. Numerous mechanisms including epigenetic regulation modulate the correct progress of this process. Dietary exposures occurring over a specific period of time might cause long-lasting and even permanent changes in gene expression regulated by epigenetic mechanisms. For that reason, we investigated the adipogenesis of 3 T3-L1 cells with the excess of saturated and monounsaturated fatty acids and their influence on global and site-specific DNA methylation in these cells. Materials and methods 3T3-L1 cells were cultured in vitro to obtain 100% of confluence, then the adipogenesis was induced by a differentiation cocktail with the addition of the excess of 0.25 mM and 0.5 mM of palmitic (16:0), stearic (18:0) and oleic (18:1n-9) acids. DNA and RNA were extracted at five-time points to assess the adipogenesis process. The phenotype of mature adipocytes (insulin sensitivity, adipokines secretion, fat content) was estimated in fully mature adipocytes. DNA methylation was investigated both during adipogenesis and in mature adipocytes. Results Oleic acids stimulated expression of C/ebpα and Pparγ, which was correlated with lower methylation levels at promoters sites. Furthermore, cells cultured with an excess of oleic acid were characterized by higher lipid accumulation rate, higher leptin, and lower adiponectin secretion. Moreover, in all experimental cells, insulin signaling and glucose utilization were impaired. Conclusion Oleic acid affected the methylation of Pparγ and C/ebpα promoters, what correlated with higher expression. Furthermore, examined free fatty acids influenced the phenotype of mature adipocytes, especially insulin signaling pathway and adipokine secretion.

scholarly journals Determination of Seasonal Changes on Lipid Content and Fatty Acids of Nemipterus randalli (Russell, 1986) from Mersin Bay

2020 ◽  
Vol 8 (8) ◽  
pp. 1623-1629
Author(s):  
Mısra Bakan ◽  
Nahit Soner Börekçi ◽  
Deniz Ayas
Keyword(s):  
Fatty Acids ◽  
Oleic Acid ◽  
Fatty Acid ◽  
Polyunsaturated Fatty Acids ◽  
Stearic Acid ◽  
Palmitic Acid ◽  
Lipid Content ◽  
Seasonal Changes ◽  
Monounsaturated Fatty Acids ◽  
Spring Season

In this study, the seasonal changes on lipid content and fatty acid levels of Nemipterus randalli from the Mersin Bay have been determined. Total lipid levels were found as 3.17%, 2.12%, 0.63%, and 0.72% in spring, summer, autumn and winter seasons, respectively. The fatty acid composition of this species is composed of 30 fatty acids. Major fatty acids are palmitic acid (C16:0) and stearic acid (C18:0) from saturated fatty acids (SFAs) oleic acid (C18:1n9c) and 11-docosenoic acid (ceteloic; C22:1n11) from monounsaturated fatty acids (MUFAs) and eicosapentaenoic acid (EPA; C20: 5n3), and docosahexaenoic acid (DHA; C22: 6n3) from polyunsaturated fatty acids (PUFAs). The highest level of palmitic acid was detected in the winter season, and the palmitic acid level varied between 15.41% and 20.72% (77.79-433.30 mg/100g). The highest level of stearic acid was determined in the spring season, and its levels varied between 14.75% and 19.14%, and its levels were also determined as 77.95-483.91 mg/100g. Oleic acid from the monounsaturated fatty acids varied between 5.46% and 7.98%, and its levels were found to be 31.98-224.38 mg/100g. Ceteloic acid varied between 5.73% and 7.80%, and its levels were determined to be 33.01-161.11 mg/100g. The EPA levels from the polyunsaturated fatty acids ranged from 4.34 to 5.34%, and its levels were found to be 19.30-137.50 mg/100g. The highest levels of DHA were detected in autumn, its levels varied between 21.09% and 23.00%, and its levels have also been detected as 102.30-604.25 mg/100g. The highest levels of Σn3, Σn6 and Σn9 were found in the spring season. The levels of Σn3, Σn6 and Σn9 varied between 26.73-27.19% (122.89-751.59 mg/100g), 4.19-4.79% (18.63-134.68 mg/100g) and 5.95-9.79% (35.22-247.15 mg/100g), respectively. AI and TI values in N. randalli were found at 0.28-0.36% and 0.33-0.36%, respectively.

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