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Age-related changes of vitamin E: α-tocopherol levels in plasma and various tissues of mice and hepatic α-tocopherol transfer protein

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Abstract

Purpose

Despite numerous studies on the RRR- and all-rac-α-tocopherol isoform of vitamin E (VE) during aging, this relationship has not been examined in specific tissues. Since α-tocopherol is the most abundant of VE’s eight isoforms, and VE is an important antioxidant that impacts the aging process, we analyzed α-tocopherol levels in plasma and tissues of mice at progressive ages. Moreover, we examined protein and mRNA expression levels of hepatic α-tocopherol transfer protein (α-TTP), which specifically binds α-tocopherol, during aging.

Methods

The α-tocopherol levels in plasma, liver, cerebrum, hippocampus, cerebellum, heart, kidney, epididymal adipose tissue, testis, pancreas, soleus muscle, plantaris muscle, and duodenum from male C57BL/6NCr mice at 3, 6, 12, 18, and 24 months of age were determined by HPLC and fluorescence detection. Also, hepatic α-TTP protein and mRNA expression levels were analyzed by Western blot and qPCR, respectively.

Results

Tissue-specific, age-related changes of α-tocopherol levels normalized by tissue weight were observed in the liver, cerebrum, hippocampus, cerebellum, heart, kidney, and epididymal adipose tissue. Specifically, α-tocopherol levels in epididymal adipose tissue increased greatly as mice aged from 6 to 24 months. Although hepatic α-TTP protein levels also showed age-related changes, α-TTP mRNA expression levels measured after overnight fasting were not altered.

Conclusions

In this study, we determined that α-tocopherol levels and hepatic α-TTP protein levels of mice undergo significant tissue-specific, age-related changes. This is the first report to investigate VE in terms of the α-tocopherol levels in plasma and various tissues of mice and hepatic α-TTP protein levels during aging.

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Abbreviations

ABCA1:

ATP-binding cassette subfamily A, member 1

ANOVA:

One-way analysis of variance

C/EBPα:

CCAAT/enhancer binding protein α

Cyp4f14:

Cytochrome P450, family 4, subfamily f, polypeptide 14

EDTA:

Ethylenediaminetetraacetic acid

6-FAM:

5′-carboxyfluorescein

GAPDH:

Glyceraldehyde 3-phosphate dehydrogenase

HPLC:

High-performance liquid chromatography

qPCR:

Quantitative polymerase chain reaction

PIP2 :

Phosphatidylinositol bisphosphate

PPARγ:

Peroxisome proliferator-activated receptor γ

SEM:

Standard error of the mean

TG:

Triglyceride

TNFα:

Tumor necrosis factor α

α-TTP:

Alpha tocopherol transfer protein

VE:

Vitamin E

VLDL:

Very low density lipoprotein

ZEN:

N,N-diethyl-4-(4-nitronaphthalen-1-ylazo)-phenylamine

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Acknowledgments

We are grateful to Mr. H. Tamura, Eisai Food and Chemical Co., Ltd. Japan, for providing dl-tocol and α-tocopherol standards. We also thank Dr. K. Fukui, Shibaura Institute of Technology for technical assistance and Ms. P. Minick for the excellent English editorial assistance. This study is supported by Japan Society for the Promotion of Science (JSPS) KAKENHI Grant Number 24380073 (A.I.).

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Authors and Affiliations

  1. Molecular Regulation of Aging, Tokyo Metropolitan Institute of Gerontology (TMIG), 35-2 Sakae-cho, Itabashi-ku, Tokyo, 173-0015, Japan

    Keita Takahashi, Shoko Takisawa & Akihito Ishigami

  2. Department of Geriatrics and Vascular Medicine, Tokyo Medical and Dental University, Tokyo, 113-8510, Japan

    Keita Takahashi & Kentaro Shimokado

  3. Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, 113-0033, Japan

    Nozomu Kono & Hiroyuki Arai

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  1. Keita Takahashi
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  2. Shoko Takisawa
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  4. Nozomu Kono
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Correspondence to Akihito Ishigami.

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Takahashi, K., Takisawa, S., Shimokado, K. et al. Age-related changes of vitamin E: α-tocopherol levels in plasma and various tissues of mice and hepatic α-tocopherol transfer protein. Eur J Nutr 56, 1317–1327 (2017). https://doi.org/10.1007/s00394-016-1182-4

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  • DOI: https://doi.org/10.1007/s00394-016-1182-4

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