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Anti-Adipogenic and Antiviral Effects of L-Carnitine on Hepatitis C Virus Infection

Research Project

Project/Area Number 15K08980
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Gastroenterology
Research InstitutionHokkaido University

Principal Investigator

koji ogawa  北海道大学, 大学病院, 助教 (20735188)

Co-Investigator(Kenkyū-buntansha) 坂本 直哉  北海道大学, 医学研究院, 教授 (10334418)
須田 剛生  北海道大学, 大学病院, 特任助教 (20447460)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
KeywordsHCV / 肝脂肪化 / カルニチン
Outline of Final Research Achievements

We analyzed the anti-HCV activity of L-carnitine, a substance involved in the transport of fatty acids into mitochondria.Treatment of HCV JFH-1-infected cells with L-carnitine inhibited HCV propagation. In contrast, L-carnitine had no anti-HCV activity in the HCV replicon system, which is lacking viral assembly. In addition, Lcarnitine did not affect HCV entry. However, Lcarnitine treatment decreased intracellular lipid droplets, which are crucial for HCV assembly. The expression level of CPT-1 was decreased in JFH-1-infected cells, and L-carnitine treatment restored this expression.HCV-infected cells exhibited increased production of reactive oxygen species and glutathione oxidation. L-carnitine decreased oxidative stress induced by JFH-1-infection, as shown by glutathione/glutathione disulfide assays and MitoSOX staining. L-carnitine exhibited anti-HCV activity, possibly by inhibiting HCV assembly and through its anti-adipogenic activity in HCV-infected cells.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (15 results)

All 2018 2017 2016 2015

All Journal Article (14 results) (of which Peer Reviewed: 14 results,  Open Access: 7 results,  Acknowledgement Compliant: 6 results) Presentation (1 results)

  • [Journal Article] Safety and efficacy of sofosbuvir and ribavirin for genotype 2 hepatitis C Japanese patients with renal dysfunction2018

    • Author(s)
      Sho T, Suda G,, Nagasaka A, Yamamoto Y, Furuya K, Kumagai K, Uebayashi M, Terashita K, Kobayashi T, Tsunematsu I, Onodera M, Meguro T, Kimura M, Ito J, Umemura M, Izumi T, Kawagishi N, Ohara M, Ono Y, Nakai M, Natsuizaka M, Morikawa K, Ogawa K, Sakamoto N
    • Journal Title

      Heptology Research

      Volume: in press Issue: 7 Pages: 529-538

    • DOI

      10.1111/hepr.13056

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Treatment of hepatitis C in special populations.2018

    • Author(s)
      Suda G, Ogawa K, Morikawa K, Sakamoto N
    • Journal Title

      Journal of Gastroenterology

      Volume: in press Issue: 5 Pages: 591-605

    • DOI

      10.1007/s00535-017-1427-x

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Increased serum C-reactive protein and decreased urinary aquaporin 2 levels are predictive of the efficacy of tolvaptan in patients with liver cirrhosis.2018

    • Author(s)
      3.Nakai M, Ogawa K, Takeda R, Ohara M, Kawagishi N, Izumi T, Umemura M, Ito J, Sho T, Suda G, Morikawa K, Sakamoto N
    • Journal Title

      Hepatology Research

      Volume: in press

    • NAID

      120006551584

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Add-on effects of fluvastatin in simeprevir/pegylated-interferon/ribavirin combination therapy for patients with genotype 1 hepatitis C virus infection: A randomized controlled study2017

    • Author(s)
      5.Suda G, Ito J, Nagasaka A, Yamamoto Y, Furuya K, Okamoto M, Terashita K, Kobayashi T, Tsunematsu I, Yoshida J, Meguro T, Ohara M, Kawagishi N, Kimura M, Umemura M, Izumi T, Tsukuda Y, Nakai M, Sho T, Natsuizaka M, Morikawa K, Ogawa K, Sakamoto N
    • Journal Title

      Hepatology Research

      Volume: 48

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Retreatment with sofosbuvir, ledipasvir, and add-on ribavirin for patients who failed daclatasvir and asunaprevir combination therapy2017

    • Author(s)
      Suda G, Ogawa K, Yamamoto Y, Katagiri M, Furuya K, Kumagai K, Konno J, Kimura M, Kawagishi N, Ohara M, Umemura M, Ito J, Izumi T, Nakai M, Sho T, Natsuizaka M, Morikawa K, Tsubota A, Shimada N, Iio E, Tanaka Y, Sakamoto N; NORTE Study Group.
    • Journal Title

      J Gastroenterol

      Volume: 印刷中 Issue: 10 Pages: 1122-1129

    • DOI

      10.1007/s00535-017-1328-z

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Safety and efficacy of daclatasvir and asunaprevir in hepatitis C virus infected patients with renal impairment2017

    • Author(s)
      Suda G, Nagasaka A, Yamamoto Y, Furuya K, Kumagai K, Kudo M, Terashita K, Kobayashi T, Tsunematsu I, Yoshida J, Meguro T, Kimura M, Ito J, Umemura M, Izumi T, Tsunematsu S, Sato F, Tsukuda Y, Nakai M, Sho T, Natsuizaka M, Morikawa K, Ogawa K, Sakamoto N; NORTE Study Group.
    • Journal Title

      Hepatol Res

      Volume: 印刷中 Issue: 11 Pages: 1127-1136

    • DOI

      10.1111/hepr.12851

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Novel Treatment of Hepatitis C Virus Infection for Patients with Renal Impairment2016

    • Author(s)
      Suda G, Ogawa K, Kimura M, Nakai M, Sho T, Morikawa K, Sakamoto N.
    • Journal Title

      J Clin Transl Hepatol

      Volume: 4(4) Pages: 320-327

    • DOI

      10.14218/jcth.2016.00032

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Anti-adipogenic and antiviral effects of l-carnitine on hepatitis C virus infection.2016

    • Author(s)
      Tsukuda Y, Suda G, Tsunematsu S, Ito J, Sato F, Terashita K, Nakai M, Sho T, Maehara O, Shimazaki T, Kimura M, Morikawa K, Natsuizaka M, Ogawa K, Ohnishi S, Chuma M, Sakamoto N
    • Journal Title

      J Med Virol

      Volume: 89 Issue: 5 Pages: 857-866

    • DOI

      10.1002/jmv.24692

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] ZEB1 expression is associated with prognosis of intrahepatic cholangiocarcinoma2016

    • Author(s)
      Terashita K, Chuma M, Hatanaka Y, Hatanaka K, Mitsuhashi T, Yokoo H, Ohmura T, Ishizu H, Muraoka S, Nagasaka A, Tsuji T, Yamamoto Y, Kurauchi N, Shimoyama N, Toyoda H, Kumada T, Kaneoka Y, Maeda A, Ogawa K, Natsuizaka M, Kamachi H, Kakisaka T, Kamiyama T, Taketomi A, Matsuno Y, Sakamoto N
    • Journal Title

      J Clin Pathol

      Volume: in press Issue: 7 Pages: 593-599

    • DOI

      10.1136/jclinpath-2015-203115

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Prevalence and characteristics of naturally occurring sofosbuvir resistance-associated variants in patients with hepatitis C virus genotype 1b infection2016

    • Author(s)
      Ito J, Suda G, Yamamoto Y, Nagasaka A, Furuya K, Kumagai K, Kikuchi H, Miyagishima T, Kobayashi T, Kimura M, Yamasaki K, Umemura M, Izumi T, Tsunematsu S, Sato F, Tsukuda Y, Terashita K, Nakai M, Sho T, Natsuizaka M, Morikawa K, Ogawa K, Sakamoto
    • Journal Title

      Hepatol Res

      Volume: in press Issue: 13 Pages: 1294-1303

    • DOI

      10.1111/hepr.12685

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Efficacy and safety of daclatasvir and asunaprevir combination therapy in chronic hemodialysis patients with chronic hepatitis C.2016

    • Author(s)
      Suda G, Kudo M, Nagasaka A, Furuya K, Yamamoto Y, Kobayashi T, Shinada K, Tateyama M, Konno J, Tsukuda Y, Yamasaki K, Kimura M, Umemura M, Izumi T, Tsunematsu S, Sato F, Terashita K, Nakai M, Horimoto H, Sho T, Natsuizaka M, Morikawa K, Ogawa K, Sakamoto N
    • Journal Title

      J Gastroenterol

      Volume: in press

    • NAID

      120006313426

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Serum granulysin levels as a predictor of serious telaprevir-induced dermatological reactions.2015

    • Author(s)
      Suda G, Yamamoto Y, Nagasaka A, Furuya K, Kudo M, Chuganji Y, Tsukuda Y, Tsunematsu S, Sato F, Terasita K, Nakai M, Horimoto H, Sho T, Natsuizaka M, Ogawa K, Ohnishi S, Chuma M, Fujita Y, Abe R, Taniguchi M, Nakagawa M, Asahina Y, Sakamoto N
    • Journal Title

      Hepatol Res

      Volume: 印刷中 Issue: 8 Pages: 837-45

    • DOI

      10.1111/hepr.12421

    • NAID

      120005820706

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Intratumoral artery on contrast-enhanced computed tomography imaging: differentiating intrahepatic cholangiocarcinoma from poorly differentiated hepatocellular carcinoma2015

    • Author(s)
      Tsunematsu S, Chuma M, Kamiyama T, Miyamoto N, Yabusaki S, Hatanaka K, Mitsuhashi T, Kamachi H, Yokoo H, Kakisaka T, Tsuruga Y, Orimo T, Wakayama K, Ito J, Sato F, Terashita K, Nakai M, Tsukuda Y, Sho T, Suda G, Morikawa K, Natsuizaka M, Nakanishi M, Ogawa K, Taketomi A, Matsuno Y, Sakamoto N
    • Journal Title

      Abdom Imaging

      Volume: 40 Issue: 6 Pages: 1492-9

    • DOI

      10.1007/s00261-015-0352-9

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] A pivotal role of Krüppel-like factor 5 in regulation of cancer stem-like cells in hepatocellular carcinoma.2015

    • Author(s)
      Maehara O, Sato F, Natsuizaka M, Asano A, Kubota Y, Itoh J, Tsunematsu S, Terashita K, Tsukuda Y, Nakai M, Sho T, Suda G, Morikawa K, Ogawa K, Chuma M, Nakagawa K, Ohnishi S, Komatsu Y, Whelan KA, Nakagawa H, Takeda H, Sakamoto N.
    • Journal Title

      Cancer Biol Ther

      Volume: 16 Issue: 10 Pages: 14531461-14531461

    • DOI

      10.1080/15384047.2015.1070992

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] 肝硬変患者に対するカルニチン製剤の有用性の検討2015

    • Author(s)
      小川浩司,梅村真知子,出水孝章,伊藤淳,常松聖司,佐藤史幸,中井正人,荘拓也,須田剛生,森川賢一,坂本直哉.
    • Organizer
      第117回日本消化器病学会北海道支部例会
    • Place of Presentation
      札幌コンベンションセンター(北海道 札幌市)
    • Year and Date
      2015-08-29
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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