Vitamin E: metabolism and molecular aspects

Torquato, Pierangelo; Marinelli, Rita; Bartolini, Desirée; Giusepponi, Danilo; Cruciani, Gabriele; Siragusa, Lydia; Galarini, Roberta; Sebastiani, Bartolomeo; Gioiello, Antimo; Galli, Francesco

doi:10.1016/b978-0-12-811907-5.00020-8

Cited by 11 publications

(19 citation statements)

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“…Cellular experiments in study further emphasizes the concept that different vitamin E derivatives have different gene regulatory functions (37,38). Compared with d-T3, the use of GA may directly modulate ApoE activity avoiding the need for an efficient bioavailability and metabolism of d-T3 to form d-T3-13'COOH in the brain.…”

Section: Discussionmentioning

confidence: 99%

Garcinoic acid prevents β-amyloid (Aβ) deposition in the mouse brain

Marinelli

Torquato

Bartolini

et al. 2020

Journal of Biological Chemistry

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Garcinoic acid (GA or δ-T3-13’COOH), is a natural vitamin E metabolite that has preliminarily been identified as a modulator of nuclear receptors involved in β-amyloid (Aβ) metabolism and progression of Alzheimer’s disease (AD). In this study, we investigated GA’s effects on Aβ oligomer formation and deposition. Specifically, we compared them with those of other vitamin E analogs and the soy isoflavone genistein, a natural agonist of peroxisome proliferator–activated receptor γ (PPARγ) that has therapeutic potential for managing AD. GA significantly reduced Aβ aggregation and accumulation in mouse cortical astrocytes. Similarly to genistein, GA up-regulated PPARγ expression and apolipoprotein E (ApoE) efflux in these cells with an efficacy that was comparable to that of its metabolic precursor δ-tocotrienol and higher than those of α-tocopherol metabolites. Unlike for genistein and the other vitamin E compounds, the GA-induced restoration of ApoE efflux was not affected by pharmacological inhibition of PPARγ activity, and specific activation of pregnane X receptor (PXR) was observed together with ApoE and multidrug resistance protein 1 (MDR1) membrane transporter up-regulation in both the mouse astrocytes and brain tissue. These effects of GA were associated with reduced Aβ deposition in the brain of TgCRND8 mice, a transgenic AD model. In conclusion, GA holds potential for preventing Aβ oligomerization and deposition in the brain. The mechanistic aspects of GA’s properties appear to be distinct from those of other vitamin E metabolites and of genistein.

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Section: Discussionmentioning

confidence: 99%

Garcinoic acid prevents β-amyloid (Aβ) deposition in the mouse brain

Marinelli

Torquato

Bartolini

et al. 2020

Journal of Biological Chemistry

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“…Such variability of α-TOH was completely corrected after normalization of the vitamin levels for the concentrations of cholesterol (ratio α-TOH/cholesterol). The latter is a major component of circulating lipoproteins, i.e., the tissue transferring system of vitamin E; therefore, such normalization helps to identify possible confounding factors deriving from both physiological and pathological variations of the lipid status (for example, unreported food intake, subclinical forms of dyslipidemia with mild hypercholesterolemia or non-alcoholic fatty liver) (extensively review elsewhere in References [ 5 , 26 ]).…”

Section: Resultsmentioning

confidence: 99%

“…In recent times, long-chain metabolites (LCMs; Figure 1 ) of vitamin E have come to the attention of the scientific community. A series of studies provided the technology to synthesize and determine these metabolites in biological systems [ 23 , 25 ], and others identified their anti-inflammatory, anti-atherogenic, and detoxification properties that are superior to those of their vitamin precursors (reviewed in References [ 26 , 27 , 28 , 29 ]). Because these metabolites have been the last to be identified and measured in human blood with standardized and validated procedures [ 23 , 30 , 31 ], their interindividual variability in response to α-TOH supplementation remains unexplored.…”

Section: Introductionmentioning

confidence: 99%

“…Metabolomics data will include the levels of the free form of polyunsaturated fatty acids (PUFAs) and their metabolites that have been included in the one-shot LC-MS/MS analysis protocol recently developed in our labs to assess the metabolome of vitamin E (VE) [ 30 ]. Leukocyte pregnane X receptor (PXR) and CYP4F2 expression will be investigated by immunoblot, these two being molecular targets of α-TOH with a proposed role in the metabolism and function of this vitamin [ 26 ].…”

Section: Introductionmentioning

confidence: 99%

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Alpha-Tocopherol Metabolites (The Vitamin E Metabolome) and Their Interindividual Variability during Supplementation

et al. 2021

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The metabolism of α-tocopherol (α-TOH, vitamin E) shows marked interindividual variability, which may influence the response to nutritional and therapeutic interventions with this vitamin. Recently, new metabolomics protocols have fostered the possibility to explore such variability for the different metabolites of α-TOH so far identified in human blood, i.e., the “vitamin E metabolome”, some of which have been reported to promote important biological functions. Such advances prompt the definition of reference values and degree of interindividual variability for these metabolites at different levels of α-TOH intake. To this end, a one-week oral administration protocol with 800 U RRR-α-TOH/day was performed in 17 healthy volunteers, and α-TOH metabolites were measured in plasma before and at the end of the intervention utilizing a recently validated LC-MS/MS procedure; the expression of two target genes of α-TOH with possible a role in the metabolism and function of this vitamin, namely pregnane X receptor (PXR) and the isoform 4F2 of cytochrome P450 (CYP4F2) was assessed by immunoblot in peripheral blood leukocytes. The levels of enzymatic metabolites showed marked interindividual variability that characteristically increased upon supplementation. With the exception of α-CEHC (carboxy-ethyl-hydroxychroman) and the long-chain metabolites M1 and α-13′OH, such variability was found to interfere with the possibility to utilize them as sensitive indicators of α-TOH intake. On the contrary, the free radical-derived metabolite α-tocopheryl quinone significantly correlated with the post-supplementation levels of α-TOH. The supplementation stimulated PXR, but not CYP4F2, expression of leucocytes, and significant correlations were observed between the baseline levels of α-TOH and both the baseline and post-supplementation levels of PXR. These findings provide original analytical and molecular information regarding the human metabolism of α-TOH and its intrinsic variability, which is worth considering in future nutrigenomics and interventions studies.

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“…these targets appear to include other nuclear receptors (e.g. PPAR-) recently reviewed elsewhere (Torquato et al, 2020) and the anti-inflammatory protein 5-lipoxygenase (Pein et al, 2018). In another example, microbiome-derived ascorbate inhibits the glucose transporter GLUT1 in human CD4 + effector T cells, inducing apoptosis (Chang et al, 2019).…”

Section: Emerging Opportunitiesmentioning

confidence: 99%