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Journal of Oleo Science 2022Brown adipose tissue (BAT) functions as a radiator for thermogenesis and helps maintain body temperature and regulate metabolism. Inflammatory signals have been reported...
Brown adipose tissue (BAT) functions as a radiator for thermogenesis and helps maintain body temperature and regulate metabolism. Inflammatory signals have been reported to inhibit PGC-1α activation and UCP1-mediated thermogenesis in brown adipocytes. Inflammation is mainly caused by cell hypertrophy and macrophage invasion due to obesity, and invading macrophages secrete inflammatory cytokines, including TNF-α, IL1β, and IL6, which suppress the thermogenesis in BAT. Tocopherol is a lipid-soluble vitamin with anti-inflammatory effects is expected to contribute to the suppression of inflammation in adipose tissue. In this study, we investigated the protective effect of tocopherols, α-tocopherol (α-toc) and δ-tocopherol (δ-toc), against brown adipocyte inflammation and thermogenesis dysfunction.Inflammatory stimulation by TNF-α, a major inflammatory cytokine, significantly decreased the protein expression levels of UCP1 and PGC-1α in rat primary brown adipocytes. The pre-incubation of α-toc or δ-toc significantly suppressed the decrease in UCP1 and PGC-1α expression and lipid accumulation. Additionally, α-toc and δ-toc suppress the induction of ERK1/2 gene expression, implying that an antiinflammatory effect is involved in this protective effect. We fed mice a high-fat diet for 16 weeks and investigated the effects of α-toc and δ-toc in the diet. Intake of α-toc and δ-toc significantly suppressed weight gain and hypertrophy of brown adipocytes. Our results suggest that α-toc and δ-toc suppress the dysfunction of thermogenesis in brown adipocytes due to inflammation and contribute to the treatment of obesity and obesity-related metabolic diseases.
Topics: Mice; Rats; Animals; Adipocytes, Brown; Uncoupling Protein 1; Tumor Necrosis Factor-alpha; Thermogenesis; Adipose Tissue, Brown; Diet, High-Fat; Obesity; Inflammation; Hypertrophy; Lipids; Mice, Inbred C57BL
PubMed: 36310052
DOI: 10.5650/jos.ess22184 -
Free Radical Biology & Medicine Nov 2021The name vitamin E, was given by Barnett and Sure who suggested that the factor proposed by Evans and Bishop as substance "X," be termed vitamin "E" as the next vitamin... (Review)
Review
The name vitamin E, was given by Barnett and Sure who suggested that the factor proposed by Evans and Bishop as substance "X," be termed vitamin "E" as the next vitamin after the A, B, C and D vitamins had been already described. The identification of vitamin E with a-tocopherol was made in 1936 by Evans' group. One year later β-tocopherol and 11 years later δ-tocopherol were isolated. Tocotrienol (named zetatocopherol) was first described in 1957 and later isolated in 1961. The antioxidant property of tocopherols was reported by Olcott and Emerson in 1937. Inherited vitamin E deficiency, AVED, characterized by a form of neuromyopathy was first described in 1981. The disease, was localized to chromosome 8q and found to be caused by a mutation of the a-TTP gene. The subsequent paragraphs are not a comprehensive review but only critical reflections on some important aspects of vitamin E research.
Topics: Antioxidants; Humans; Tocopherols; Tocotrienols; Vitamin E; Vitamin E Deficiency
PubMed: 34478835
DOI: 10.1016/j.freeradbiomed.2021.07.042 -
The Journal of Pharmacology and... Sep 2019Induction of lysosomal exocytosis alleviates lysosomal storage of undigested metabolites in cell models of lysosomal disorders (LDs). However, whether this strategy...
Induction of lysosomal exocytosis alleviates lysosomal storage of undigested metabolites in cell models of lysosomal disorders (LDs). However, whether this strategy affects other vesicular compartments, e.g., those involved in endocytosis, is unknown. This is important both to predict side effects and to use this strategy in combination with therapies that require endocytosis for intracellular delivery, such as lysosomal enzyme replacement therapy (ERT). We investigated this using -tocopherol as a model previously shown to induce lysosomal exocytosis and cell models of type A Niemann-Pick disease, a LD characterized by acid sphingomyelinase (ASM) deficiency and sphingomyelin storage. -Tocopherol and derivative CF3-T reduced net accumulation of fluid phase, ligands, and polymer particles via phagocytic, caveolae-, clathrin-, and cell adhesion molecule (CAM)-mediated pathways, yet the latter route was less affected due to receptor overexpression. In agreement, -tocopherol lowered uptake of recombinant ASM by deficient cells (known to occur via the clathrin pathway) and via targeting intercellular adhesion molecule-1 (associated to the CAM pathway). However, the net enzyme activity delivered and lysosomal storage attenuation were greater via the latter route. Data suggest stimulation of exocytosis by tocopherols is not specific of lysosomes and affects endocytic cargo. However, this effect was transient and became unnoticeable several hours after tocopherol removal. Therefore, induction of exocytosis in combination with therapies requiring endocytic uptake, such as ERT, may represent a new type of drug interaction, yet this strategy could be valuable if properly timed for minimal interference.
Topics: Animals; Cell Adhesion Molecules; Cells, Cultured; Combined Modality Therapy; Drug Interactions; Endocytosis; Enzyme Replacement Therapy; Exocytosis; Humans; Nanoparticles; Niemann-Pick Disease, Type A; Recombinant Proteins; Sphingomyelin Phosphodiesterase; Tocopherols
PubMed: 31101681
DOI: 10.1124/jpet.119.257345 -
Molecules (Basel, Switzerland) Oct 2020This investigation included the chemical analysis of () seed oil and its antifungal properties against 10 fungal species. Seed oils of six populations were analyzed...
This investigation included the chemical analysis of () seed oil and its antifungal properties against 10 fungal species. Seed oils of six populations were analyzed using high performance liquid chromatography (HPLC) and gas chromatograph/mass spectrometry (GC-MS). The HPLC analysis indicated that . seed oil exhibited a very high level of tocopherol contents, with values in the range of 2385.66-2722.68 mg/100 g. The most abundant tocopherol isomer was δ-tocopherol (90.39%), followed by γ-tocopherol (8.08%) and α-tocopherol (1.14%). We discovered for the first time the presence of tocotrenols in seed oils of the six populations studied. The GC-MS analyses revealed that linoleic acid was the main fatty acid (65.17%), followed by oleic acid (23.12%), palmitic acid (5.36%) and stearic acid (3.08%). We also studied the antifungal activity of seed oil of the Medenine (MD) population on ten fungal pathogens. The antifungal effects differed among pathogens and depended on oil concentrations. Seed oil of the MD population caused a significant decrease in mycelial growth of all fungi tested, with values ranging 31.50-82.11%, except for sp., which showed no inhibition. The antifungal activity against the 10 selected fungi can be explained by the richness in tocols of the extracted oil and make a promising crop for biological control. Furthermore, the importance of fatty acids and the wide geographic spread in Tunisia of this species make this crop a potential source of renewable energy.
Topics: Antifungal Agents; Fungi; Gas Chromatography-Mass Spectrometry; Linoleic Acid; Oleic Acid; Palmitic Acid; Peganum; Plant Oils; Seeds; Tocopherols
PubMed: 33036316
DOI: 10.3390/molecules25194569 -
Evidence-based Complementary and... 2022Uremic pruritus is a frequent and prominent symptom in patients with advanced or end-stage renal disease. Lack of an effective treatment for kidney disease-associated... (Review)
Review
Uremic pruritus is a frequent and prominent symptom in patients with advanced or end-stage renal disease. Lack of an effective treatment for kidney disease-associated pruritus often leads to many problems for these patients and makes it difficult to choose an appropriate treatment. The purpose of this evidence-based hypothesis is to share the scientific reasons and related mechanisms in order to claim that lettuce could be useful in the treatment of uremic pruritus. This hypothesis is based on studies related to lettuce and its anti-inflammatory, antioxidant, antidiabetic, sedative, hypnotic, nephroprotective, potassium balancing, and blood purification properties. As a result, we suggest that lettuce could be a good choice for improving and reducing uremic pruritus due to its certain characteristics. Although proof of this hypothesis requires further clinical trial studies, this hypothesis can nevertheless lead to formulating an appropriate therapy for uremic-induced pruritus. By conducting a molecular docking study, we investigated the interactions between nineteen natural bioactive components of lettuce () and human kappa opioid receptors. The docking studies revealed that most of the ligands showed better antipruritic efficacy than gabapentin. Gamma-tocopherol, delta-tocopherol, and campesterol demonstrated the highest binding affinities toward the target protein.
PubMed: 35392648
DOI: 10.1155/2022/4231854 -
Foods (Basel, Switzerland) Jun 2022This study was the first time the effects of pretreatment technology (microwave roasting, MR; oven roasting, OR; steaming roasting, SR) and processing technology (screw...
This study was the first time the effects of pretreatment technology (microwave roasting, MR; oven roasting, OR; steaming roasting, SR) and processing technology (screw pressing, SP; aqueous enzymatic extraction, AEE; subcritical butane extraction, SBE) on the quality (physicochemical properties, phytochemical content, and antioxidant ability) of walnut oil were systematically compared. The results showed that the roasting pretreatment would reduce the lipid yield of walnut oil and SBE (59.53−61.19%) was the processing method with the highest yield. SR-AEE oil provided higher acid value (2.49 mg/g) and peroxide value (4.16 mmol/kg), while MR-SP oil had the highest content of polyunsaturated fatty acid (73.69%), total tocopherol (419.85 mg/kg) and total phenolic compounds (TPC, 13.12 mg/kg). The DPPH-polar and ABTS free radicals’ scavenging abilities were accorded with SBE > AEE > SP. SBE is the recommended process for improving the extraction yield and antioxidant ability of walnut oil. Hierarchical cluster analysis showed that processing technology had a greater impact on walnut oil than pretreatment technology. In addition, multiple linear regression revealed C18:0, δ-tocopherol and TPC had positive effects on the antioxidant ability of walnut oil, while C18:1n-9, C18:3n-3 and γ-tocopherol were negatively correlated with antioxidant activity. Thus, this a promising implication for walnut oil production.
PubMed: 35741896
DOI: 10.3390/foods11121698 -
International Journal of Molecular... Jan 2023Tocopherols are natural bioactive compounds with several health benefits. This study evaluated the effect of different ratios of α- and δ- tocopherol homologs to...
Evaluation of the Efficacy and Synergistic Effect of α- and δ-Tocopherol as Natural Antioxidants in the Stabilization of Sunflower Oil and Olive Pomace Oil during Storage Conditions.
Tocopherols are natural bioactive compounds with several health benefits. This study evaluated the effect of different ratios of α- and δ- tocopherol homologs to protect sunflower oil (SO) and olive pomace oil (OPO) against oxidation. A synergistic effect was recorded when the two tocopherols were combined at a ratio of 7:1 (α-T/δ-T). The oil samples were exposed to accelerated oxidation conditions using a Rancimat (90 °C and airflow of 15 L/h for 24 h) and protection from tocopherols was compared with that from butylated hydroxytoluene (BHT). Assessment of oil stability was examined using well-known parameters such as peroxide value (PV), thiobarbituric acid reactive substances (TBARS), p-anisidine value (p-AV), conjugated dienes (CD) and trienes (CT), and total oxidation (Totox) value, which were all significantly reduced when tocopherols were added at a ratio of 7:1 α-T/δ-T. Primary oxidative compounds measured according to PV were only reduced in SO samples (6.11%). Off-flavor compounds measured via TBARS assay in SO samples were reduced by above 20%, while p-AV was also reduced. CDvalue was correlated with PV in SO samples, while the 7:1 mixture was more effective than BHT for CTvalue. Total oxidation values in SO samples and OPO samples were reduced by 6.02% and 12.62%, respectively. These values in SO samples also provided a remarkable correlation (R2 > 0.95) with incubation time. Moreover, the synergistic effect was not only effective in reducing the oxidation values of oil samples, but also in lowering the degradation rate of tocopherols. Protective effects from tocopherols were mainly observed in SO samples, as OPO samples were more resistant to oxidation processes. This effect was even observed in fatty acid analysis, where the 7:1 mixture provided better results than BHT-spiked samples. Thus, it is suggested that tocopherol mixtures might be used as a natural preservative in the food industry to restrain lipid oxidation processes.
Topics: Antioxidants; Sunflower Oil; Olive Oil; Thiobarbituric Acid Reactive Substances; Tocopherols; Oxidation-Reduction; Plant Oils
PubMed: 36674630
DOI: 10.3390/ijms24021113 -
Plant Physiology Nov 2019Tocopherols are lipid-soluble antioxidants synthesized in plastids of plants and other photosynthetic organisms. The four known tocopherols, α-, β-, γ-, and...
Tocopherols are lipid-soluble antioxidants synthesized in plastids of plants and other photosynthetic organisms. The four known tocopherols, α-, β-, γ-, and δ-tocopherol, differ in number and position of methyl groups on their chromanol head group. In unstressed Arabidopsis () leaves, α-tocopherol constitutes the main tocopherol form, whereas seeds predominantly contain γ-tocopherol. Here, we show that inoculation of Arabidopsis leaves with the bacterial pathogen induces the expression of genes involved in early steps of tocopherol biosynthesis and triggers strong accumulation of γ-tocopherol, moderate production of δ-tocopherol, and generation of the benzoquinol precursors of tocopherols. The pathogen-inducible biosynthesis of tocopherols is promoted by the immune regulators ENHANCED DISEASE SUSCEPTIBILITY1 and PHYTOALEXIN-DEFICIENT4. In addition, tocopherols accumulate in response to bacterial flagellin and reactive oxygen species. By quantifying tocopherol forms in inoculated wild-type plants and biosynthetic pathway mutants, we provide biochemical insights into the pathogen-inducible tocopherol pathway. Notably, () mutant plants, which are compromised in both tocopherol and benzoquinol precursor accumulation, exhibit increased susceptibility toward compatible and possess heightened levels of markers of lipid peroxidation after bacterial infection. The deficiency of triunsaturated fatty acids in () quadruple mutants prevents increased lipid peroxidation in the background and restores pathogen resistance to wild-type levels. Therefore, the tocopherol biosynthetic pathway positively influences salicylic acid accumulation and guarantees effective basal resistance of Arabidopsis against compatible , possibly by protecting leaves from the pathogen-induced oxidation of trienoic fatty acid-containing lipids.
Topics: Arabidopsis; Arabidopsis Proteins; Carboxylic Ester Hydrolases; DNA-Binding Proteins; Gene Expression Regulation, Plant; Plant Immunity; Plant Leaves; Pseudomonas syringae; Tocopherols
PubMed: 31515446
DOI: 10.1104/pp.19.00618 -
Free Radical Biology & Medicine Feb 2022Natural forms of vitamin E comprise four tocopherols and four tocotrienols. During the last twenty years, there have been breakthroughs in our understanding of vitamin E...
Natural forms of vitamin E comprise four tocopherols and four tocotrienols. During the last twenty years, there have been breakthroughs in our understanding of vitamin E metabolism and biological activities of vitamin E metabolites. Research has established that tocopherols and tocotrienols are metabolized via ω-hydroxylase (CYP4F2)-initiated side chain oxidation to form 13'-hydroxychromanol and 13'-carobyxychromanol (13'-COOH). 13'-COOHs are further metabolized via β-oxidation and sulfation to intermediate carboxychromanols, terminal metabolite carboxyethyl-hydroxychroman (CEHC), and sulfated analogs. Animal and human studies show that γ-, δ-tocopherol and tocotrienols are more extensively metabolized than α-tocopherol (αT), as indicated by higher formation of CEHCs and 13'-COOHs from non-αT forms than those from αT. 13'-COOHs are shown to be inhibitors of cyclooxygenase-1/-2 and 5-lipoxygenase and much stronger than CEHCs for these activities. 13'-COOHs inhibit cancer cell growth, modulate cellular lipids and activate peroxisome proliferator-activated receptor-γ and pregnane X receptor. Consistent with mechanistic findings, αT-13'-COOH or δTE-13'-COOH, respective metabolites of αT or δ-tocotrienol, show anti-inflammatory and cancer-preventive effects, modulates the gut microbiota and prevents β-amyloid formation in mice. Therefore, 13'-COOHs are a new class of bioactive compounds with anti-inflammatory and anti-cancer activities and potentially capable of modulating lipid and drug metabolism. Based on the existing evidence, this author proposes that metabolites may contribute to disease-preventing effects of γ-, δ-tocopherol and tocotrienols. The role of metabolites in αT's actions may be somewhat limited considering controlled metabolism of αT because of its association with tocopherol-transport protein and less catabolism by CYP4F2 than other vitamin E forms.
Topics: Animals; Mice; Neoplasms; Tocopherols; Tocotrienols; Vitamin E; alpha-Tocopherol
PubMed: 34785321
DOI: 10.1016/j.freeradbiomed.2021.11.012 -
Frontiers in Cellular Neuroscience 2022The amyloid precursor protein (APP) processing pathway was altered in Alzheimer's disease (AD) and contributed to abnormal amyloid-beta (Aβ) production, which forms...
The amyloid precursor protein (APP) processing pathway was altered in Alzheimer's disease (AD) and contributed to abnormal amyloid-beta (Aβ) production, which forms insoluble interneuron protein aggregates known as amyloid plaques in the brain. Targeting the APP processing pathway is still fundamental for AD modifying therapy. Extensive research has evaluated the protective effects of vitamin E as an antioxidant and as a signaling molecule. The present study aimed to investigate the modulatory effects of different tocopherol isomers on the expression of genes involved in regulating the APP processing pathway . The screening for the effective tocopherol isomers in reducing APP expression and Aβ-42 was carried out in SH-SY5Y stably overexpressed APP Swedish. Subsequently, quantitative one-step real-time PCR was performed to determine the modulatory effects of selected tocopherol isomers on the expression of genes in SH-SY5Y stably overexpressed three different types of APP (wild-type, APP Swedish, and APP Swedish/Indiana). Our results showed that all tocopherol isomers, especially at higher concentrations (80-100 μM), significantly increased ( < 0.05) the cell viability in all cells group, but only α-tocopherol (ATF) and γ-tocopherol (GTF) significantly decreased ( < 0.05) the APP mRNA level without statistically significant APP protein level, accompanied with a reduced significance ( < 0.05) on the level of Aβ-42 in SH-SY5Y APP Swedish. On the other hand, β- and δ-tocopherol (BTF and DTF) showed no effects on the level of APP expression and Aβ-42. Subsequent results demonstrated that ATF and GTF significantly decreased ( < 0.05) the expression of gene beta-site APP cleaving enzyme (), , and Nicastrin (), but significantly increased ( < 0.05) the expression of Sirtuin 1 () in SH-SY5Y stably expressed the mutant APP form. These findings suggested that ATF and GTF could modulate altered pathways and may help ameliorate the burden of amyloid load in AD.
PubMed: 35614968
DOI: 10.3389/fncel.2022.846459