European Journal of Nutrition

, Volume 56, Issue 3, pp 1317–1327 | Cite as

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

  • Keita Takahashi
  • Shoko Takisawa
  • Kentaro Shimokado
  • Nozomu Kono
  • Hiroyuki Arai
  • Akihito IshigamiEmail author
Original Contribution



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.


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.


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.


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.


Vitamin E α-Tocopherol α-Tocopherol transfer protein Aging Liver 



ATP-binding cassette subfamily A, member 1


One-way analysis of variance


CCAAT/enhancer binding protein α


Cytochrome P450, family 4, subfamily f, polypeptide 14


Ethylenediaminetetraacetic acid




Glyceraldehyde 3-phosphate dehydrogenase


High-performance liquid chromatography


Quantitative polymerase chain reaction


Phosphatidylinositol bisphosphate


Peroxisome proliferator-activated receptor γ


Standard error of the mean




Tumor necrosis factor α


Alpha tocopherol transfer protein


Vitamin E


Very low density lipoprotein





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.).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

394_2016_1182_MOESM1_ESM.pdf (522 kb)
Supplementary material 1 (PDF 522 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Keita Takahashi
    • 1
    • 2
  • Shoko Takisawa
    • 1
  • Kentaro Shimokado
    • 2
  • Nozomu Kono
    • 3
  • Hiroyuki Arai
    • 3
  • Akihito Ishigami
    • 1
    Email author
  1. 1.Molecular Regulation of AgingTokyo Metropolitan Institute of Gerontology (TMIG)TokyoJapan
  2. 2.Department of Geriatrics and Vascular MedicineTokyo Medical and Dental UniversityTokyoJapan
  3. 3.Graduate School of Pharmaceutical SciencesUniversity of TokyoTokyoJapan

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