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Elucidation of mechanism on hepatitis C-related liver cancer exacerbation by trans-fatty acid toxicity and development of preventive method

Research Project

Project/Area Number 16K08616
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pathological medical chemistry
Research InstitutionShinshu University

Principal Investigator

AOYAMA Toshifumi  信州大学, 学術研究院医学系, 教授 (50231105)

Co-Investigator(Kenkyū-buntansha) 田中 直樹  信州大学, 学術研究院医学系, 准教授 (80419374)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsHCV / トランス脂肪酸 / 肝がん / C型肝炎ウイルスコア蛋白 / PPARalpha / デオキシコール酸 / トランス脂肪酸食 / 肝臓非癌部・癌部 / スルファチド / 脂質 / 発癌 / C型肝炎
Outline of Final Research Achievements

Transgenic mice expressing the hepatitis C virus core protein develop liver cancer at a frequency of about 30-35% at around 18 months of age. We fed 12-13-month-old male transgenic mice with a diet containing trans-fatty acids for 5 months and found liver tumors in all of these mice, demonstrating the strong liver tumorigenic effect of trans-fatty acids. These transgenic mice fed a trans-fatty acid-rich diet also showed marked hepatic steatosis, inflammation, and fibrosis in their non-tumorous liver tissues, which accompanied with activated inflammatory signaling, increased oxidative and endoplasmic reticulum stress, and accelerated cell proliferation. These changes likely contributed to promotion of liver tumorigenesis by trans-fatty acid-rich diet.

Academic Significance and Societal Importance of the Research Achievements

多くの加工食品に含まれるトランス脂肪酸は、健常人に対して、LDLコレステロールの増加に伴う心血管疾患のリスクを増加させ、また、肥満・アレルギー性疾患・認知症等を誘発する毒性を示すことが知られている。しかし、肝発癌に与える影響は明らかにされていない。本研究から、トランス脂肪酸がHCV関連肝癌の発症リスクを高める可能性が初めて示唆された。HCV持続感染者ではトランス脂肪酸の摂取量を制限することが肝発癌抑制に有効である可能性が期待される。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (2 results)

All 2019 2016

All Journal Article (2 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Open Access: 1 results)

  • [Journal Article] A high-cholesterol diet promotes steatohepatitis and liver tumorigenesis in HCV core gene transgenic mice.2019

    • Author(s)
      Wang X, Tanaka N, Hu X, Kimura T, Lu Y, Jia F, Sato Y, Nakayama J, Moriya K, Koike K, Aoyama T
    • Journal Title

      Arch Toxicol.

      Volume: in press Issue: 6 Pages: 1713-1725

    • DOI

      10.1007/s00204-019-02440-7

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Age-dependent PPARα activation induces hepatic sulfatide accumulation in transgenic mice carrying the hepatitis C virus core gene.2016

    • Author(s)
      Tian Y, Yang Y, Zhang X, Nakajima T, Tanaka N, Sugiyama E, Kamijo Y, Lu Y, Moriya K, Koike K, Gonzalez FJ, Aoyama T.
    • Journal Title

      Glycoconj J

      Volume: 33 Issue: 6 Pages: 927-936

    • DOI

      10.1007/s10719-016-9703-1

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research

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Published: 2016-04-21   Modified: 2020-03-30  

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