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Journal of Oleo Science Feb 2021This study aimed to compare the distribution of vitamin E analogs, particularly α-tocopherol and δ-tocopherol, in mice fed with a normal diet and a high-fat and...
This study aimed to compare the distribution of vitamin E analogs, particularly α-tocopherol and δ-tocopherol, in mice fed with a normal diet and a high-fat and high-sucrose diet separately. We used male C57BL/6JJcl strain mice, which were divided into six groups (control [C], Cα, Cδ, high-fat and high-sucrose [H], Hα, and Hδ groups) and bred for 4 weeks. The additional quantity of α-tocopherol or E-mix D (containing 86.7% δ-tocopherol) into diet was 800 mg/kg diet. The final body weight was significantly higher in the H group than in the C group. However, the effects of vitamin E analog intake had no significant difference, with no synergy between vitamin E and diet. Similar results were obtained in epididymal fat weight. Moreover, α-tocopherol was mainly distributed in the liver in both the Cα group and Hα group, whereas δ-tocopherol mostly accumulated in the epididymal fat, in both the Cδ group and Hδ group. Also, δ-tocopherol was detected in all tissues in both groups. Both the α-tocopherol and δ-tocopherol levels in the epididymal fat were significantly lower in the H group than in the C group. In conclusion, our results suggest that a portion of δ-tocopherol was incorporated into the adipose tissue by chylomicron before arriving at the liver, and then it is metabolized in the liver.
Topics: Adipose Tissue; Animals; Chylomicrons; Diet, Carbohydrate Loading; Diet, High-Fat; Dietary Sucrose; Liver; Male; Mice, Inbred C57BL; Tocopherols; Vitamin E; alpha-Tocopherol; Mice
PubMed: 33456009
DOI: 10.5650/jos.ess20254 -
Natural Product Research Nov 2022From an ethyl acetate-soluble fraction of the leaves of , one new trimeric -tocopherol derivative named as tocomuntin A (), together with three known -tocopherol...
From an ethyl acetate-soluble fraction of the leaves of , one new trimeric -tocopherol derivative named as tocomuntin A (), together with three known -tocopherol derivatives (-) were isolated. Their structures were elucidated based on the interpretation of NMR and MS spectroscopic data. In this work, -tocopherol () was found to have -glucosidase inhibitory activity for the first time (IC, 47.3 M).
Topics: Plant Extracts; Plant Leaves; Magnoliopsida; Tocopherols; Glycoside Hydrolase Inhibitors
PubMed: 34933616
DOI: 10.1080/14786419.2021.2018589 -
Critical Reviews in Food Science and... 2019Vitamin E is a lipid soluble vitamin comprising of eight natural isoforms, namely, α, β, δ, γ isoforms of tocopherol and α, β, δ, γ isoforms of tocotrienol. Many... (Review)
Review
Vitamin E is a lipid soluble vitamin comprising of eight natural isoforms, namely, α, β, δ, γ isoforms of tocopherol and α, β, δ, γ isoforms of tocotrienol. Many studies have been performed to elucidate its role in cancer. Until last decade, major focus was on alpha tocopherol and its anticancer effects. However, major clinical trials using alpha-tocopherol like SELECT trial and ATBC trial did not yield meaningful results. Hence there was a shift of focus to gamma-tocopherol, delta-tocopherol and tocotrienol. Unlike alpha-tocopherol, gamma-tocopherol and delta-tocopherol can scavenge reactive nitrogen species in addition to reactive oxygen species. Antiangiogenic effect, inhibition of HMG CoA reductase enzyme and inhibition of NF-κB pathway make the anti-cancer effects of tocotrienols unique compared to other vitamin E isoforms. Preclinical research on non-alpha tocopherol isoforms of vitamin E showed promising data on their anticancer effects. In this review, we deal with the current understanding on the potential mechanisms involved in the anticancer effects of vitamin E and the controversies in this field over last three decades. We also highlight the need to conduct further research on the anticancer effects of non-alpha-tocopherol isoforms in larger population and clinical setting.
Topics: Antineoplastic Agents; Clinical Trials as Topic; Humans; Neoplasms; Tocotrienols; Vitamin E; alpha-Tocopherol; gamma-Tocopherol
PubMed: 29746786
DOI: 10.1080/10408398.2018.1474169 -
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 -
Journal of Oleo Science Sep 2021The study aim was to evaluate the potential anti-inflammatory effects of vitamin E analogs, especially α-tocopherol and δ-tocopherol. We used male C57BL/6JJcl mice,...
The study aim was to evaluate the potential anti-inflammatory effects of vitamin E analogs, especially α-tocopherol and δ-tocopherol. We used male C57BL/6JJcl mice, which were divided into four groups: the control (C), high-fat and high-sucrose diet (H), high-fat and high-sucrose diet+α-tocopherol (Ha) and high-fat and high-sucrose diet+δ-tocopherol (Hd) groups. The mice were fed for 16 weeks. To the high-fat and high-sucrose diet, 800 mg/kg of α-tocopherol or δ-tocopherol was added more. The final body weight was significantly higher in the H group than in the C group. On the other hand, the final body weight was drastically lower in the Ha group and Hd group than in the H group. However, the energy intake was not significantly different among all groups. Therefore, we assumed that α-tocopherol and δ-tocopherol have potential anti-obesity effect. Besides, inflammatory cytokine gene expression was significantly higher in the epididymal fat of the H group than in the C group. These results showed that inflammation was induced by epididymal fat of mice fed a high-fat and high-sucrose diet for 16 weeks. Unfortunately, addition of α-tocopherol or δ-tocopherol to the diet did not restrain inflammation of epididymal fat. Investigation of the anti-inflammatory effects of α-tocopherol or δ-tocopherol in co-cultured 3T3-L1 cells and RAW264.7 cells showed that δ-tocopherol inhibited increased gene expression of the inflammatory cytokines, IL-1β, IL-6, and iNOS. These results suggest that an anti-inflammatory effect in the δ-tocopherol is stronger than that in the α-tocopherol in vitro. We intend to perform an experiment by in vivo sequentially in the future.
Topics: 3T3-L1 Cells; Adipocytes; Adipose Tissue; Animals; Anti-Inflammatory Agents; Anti-Obesity Agents; Body Weight; Diet, High-Fat; Dietary Sucrose; Gene Expression; Inflammation; Inflammation Mediators; Interleukin-1beta; Interleukin-6; Male; Mice; Mice, Inbred C57BL; Nitric Oxide Synthase Type II; RAW 264.7 Cells; Tocopherols; alpha-Tocopherol
PubMed: 34373409
DOI: 10.5650/jos.ess21124 -
Molecular Carcinogenesis Nov 2016The cancer preventive activity of vitamin E is suggested by epidemiological studies and supported by animal studies with vitamin E forms, γ-tocopherol and δ-tocopherol...
The cancer preventive activity of vitamin E is suggested by epidemiological studies and supported by animal studies with vitamin E forms, γ-tocopherol and δ-tocopherol (δ-T). Several recent large-scale cancer prevention trials with high dose of α-tocopherol, however, yielded disappointing results. Whether vitamin E prevents or promotes cancer is a serious concern. A better understanding of the molecular mechanisms of action of the different forms of tocopherols would enhance our understanding of this topic. In this study, we demonstrated that δ-T was the most effective tocopherol form in inhibiting prostate cancer cell growth, by inducing cell cycle arrest and apoptosis. By profiling the effects of δ-T on the cell signaling using the phospho-kinase array, we found that the most inhibited target was the phosphorylation of AKT on T308. Further study on the activation of AKT by EGFR and IGFR revealed that δ-T attenuated the EGF/IGF-induced activation of AKT (via the phosphorylation of AKT on T308 induced by the activation of PIK3). Expression of dominant active PIK3 and AKT in prostate cancer cell line DU145 in which PIK3, AKT, and PTEN are wild type caused the cells to be reflectory to the inhibition of δ-T, supporting that δ-T inhibits the PIK3-mediated activation of AKT. Our data also suggest that δ-T interferes with the EGF-induced EGFR internalization, which leads to the inhibition of the receptor tyrosine kinase-dependent activation of AKT. In summary, our results revealed a novel mechanism of δ-T in inhibiting prostate cancer cell growth, supporting the cancer preventive activity δ-T. © 2015 Wiley Periodicals, Inc.
Topics: Cell Cycle; Cell Line, Tumor; Cell Proliferation; Cell Survival; ErbB Receptors; Gene Expression Regulation, Neoplastic; Humans; Male; PTEN Phosphohydrolase; Phosphorylation; Prostatic Neoplasms; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-akt; Signal Transduction; Tocopherols
PubMed: 26465359
DOI: 10.1002/mc.22422 -
Carcinogenesis Feb 2018The PTEN/PI3K/AKT axis plays a critical role in regulating cell growth, differentiation and survival. Activation of this signaling pathway is frequently found in human...
The PTEN/PI3K/AKT axis plays a critical role in regulating cell growth, differentiation and survival. Activation of this signaling pathway is frequently found in human cancers. Our previous studies demonstrated that δ-tocopherol (δ-T) attenuates the activation of AKT by growth factor in prostate cancer cell lines, leading to inhibition of proliferation and induction of apoptosis. Herein, we investigated whether δ-T inhibits the development of prostate adenocarcinoma in prostate-specific Pten-/- (Ptenp-/-) mice in which the activation of AKT is the major driving force for tumorigenesis. By feeding Ptenp-/- mice with AIN93M or 0.2% δ-T supplemented diet starting at the age of 6 or 12 weeks, we found that δ-T treatment reduced prostate adenocarcinoma multiplicity at the age of 40 weeks by 53.3 and 42.7%, respectively. Immunohistochemical (IHC) analysis demonstrated that the phosphorylation of AKT (T308) was reduced in the prostate of the mice administered the δ-T diet. Consistently, proliferation was reduced and apoptosis was increased in prostate lesions of mice on the δ-T diet. Oxidative stress, as determined by IHC staining of 8-OH-dG, was not altered during prostate tumorigenesis, nor was it affected by administration of δ-T. In contrast, α-tocopherol (α-T) at 0.2% in the diet did not affect prostate adenocarcinoma multiplicity in the Ptenp-/- mice. This finding is consistent with data from our previous study that δ-T, but not α-T, inhibits the activation of AKT and the growth of prostate cancer cells. Together, these results demonstrate that δ-T inhibits the development of prostate adenocarcinoma in Ptenp-/- mice, mainly through inhibition of AKT activation.
Topics: Adenocarcinoma; Animals; Antioxidants; Cell Proliferation; Female; Male; Mice; Mice, Knockout; PTEN Phosphohydrolase; Phosphatidylinositol 3-Kinases; Prostatic Neoplasms; Proto-Oncogene Proteins c-akt; Tocopherols
PubMed: 29121168
DOI: 10.1093/carcin/bgx128 -
Biochemical and Biophysical Research... Nov 2018Activation of thermogenic adipocytes (brown and beige) has been considered an attractive target for weight loss and treatment of metabolic disease. Peroxisome...
Activation of thermogenic adipocytes (brown and beige) has been considered an attractive target for weight loss and treatment of metabolic disease. Peroxisome proliferator-activated receptor γ co-activator-1 α (PGC1-α) is a master regulator of thermogenic gene expression in thermogenic adipocytes. We previously reported that α-tocopherol upregulated PGC-1α gene expression and promoted thermogenic adipocyte differentiation in mammalian adipocytes. In this study, we investigated the effects of the vitamin E analogs (α-, γ- and δ-tocopherol) on PGC-1α and uncoupling protein 1 (UCP1) gene expression in 3T3-L1 cells. The expression of PGC-1α and UCP1 increased significantly with the addition of δ-tocopherol. In δ-tocopherol-treated cells, nuclear translocation of PGC-1α increased, as did p38 mitogen-activated protein kinase (MAPK) expression and phosphorylation. Our results suggest that p38 MAPK activation by δ-tocopherol contributes to PGC-1α activation and UCP1 induction.
Topics: 3T3-L1 Cells; Adipocytes, Brown; Animals; Cell Differentiation; Cell Nucleus; Cytosol; Gene Expression Regulation; Mice; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Phosphorylation; Protein Transport; Signal Transduction; Tocopherols; Uncoupling Protein 1; alpha-Tocopherol; gamma-Tocopherol; p38 Mitogen-Activated Protein Kinases
PubMed: 30336984
DOI: 10.1016/j.bbrc.2018.10.021 -
Nutrients Nov 2011Vitamin E consists of eight different variants: α-, β-, γ-, and δ-tocopherols (saturated phytyl tail) and α-, β-, γ-, and δ-tocotrienols (unsaturated phytyl... (Review)
Review
Vitamin E consists of eight different variants: α-, β-, γ-, and δ-tocopherols (saturated phytyl tail) and α-, β-, γ-, and δ-tocotrienols (unsaturated phytyl tail). Cancer prevention studies with vitamin E have primarily utilized the variant α-tocopherol. To no avail, a majority of these studies focused on variant α-tocopherol with inconsistent results. However, γ-tocopherol, and more recently δ-tocopherol, have shown greater ability to reduce inflammation, cell proliferation, and tumor burden. Recent results have shown that γ-enriched mixed tocopherols inhibit the development of mammary hyperplasia and tumorigenesis in animal models. In this review, we discuss the possible differences between the variant forms, molecular targets, and cancer-preventive effects of tocopherols. We recommend that a γ-enriched mixture, γ- and δ-tocopherol, but not α-tocopherol, are promising agents for breast cancer prevention and warrant further investigation.
Topics: Apoptosis; Breast Neoplasms; Cell Proliferation; Cyclooxygenase 2; ErbB Receptors; Female; Humans; NF-E2-Related Factor 2; PPAR gamma; Receptors, Estrogen; Tocopherols; Vitamin E; alpha-Tocopherol; gamma-Tocopherol
PubMed: 22254089
DOI: 10.3390/nu3110962 -
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