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

• Project/Area Number: 15K08980
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Hokkaido 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: ¥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)
• Keywords: HCV / 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.

Research Products

• [Journal Article] Safety and efficacy of sofosbuvir and ribavirin for genotype 2 hepatitis C Japanese patients with renal dysfunction (2018)
  • 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
  • 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
  • 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
  • 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 study (2017)
  • 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
  • Peer Reviewed
• [Journal Article] Retreatment with sofosbuvir, ledipasvir, and add-on ribavirin for patients who failed daclatasvir and asunaprevir combination therapy (2017)
  • 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
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Safety and efficacy of daclatasvir and asunaprevir in hepatitis C virus infected patients with renal impairment (2017)
  • 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
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Novel Treatment of Hepatitis C Virus Infection for Patients with Renal Impairment (2016)
  • 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
  • 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
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] ZEB1 expression is associated with prognosis of intrahepatic cholangiocarcinoma (2016)
  • 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
  • Peer Reviewed
• [Journal Article] Prevalence and characteristics of naturally occurring sofosbuvir resistance-associated variants in patients with hepatitis C virus genotype 1b infection (2016)
  • 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
  • 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
  • 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
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Intratumoral artery on contrast-enhanced computed tomography imaging: differentiating intrahepatic cholangiocarcinoma from poorly differentiated hepatocellular carcinoma (2015)
  • 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
  • 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
  • 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