Involvement of hypertension in nonalcoholic fatty liver disease via the kininogen fragment peptide

2013 Fiscal Year Final Research Report

• Project/Area Number: 23590981
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kagoshima University
• Principal Investigator: UTO Hirofumi 鹿児島大学, 医歯(薬)学総合研究科, 講師 (20347058)
• Project Period (FY): 2011 – 2013
• Keywords: NAFLD / NASH / キニノゲン / 高血圧 / 肝炎 / 肝線維化 / 脂肪肝

Research Abstract

Nonalcoholic fatty liver disease (NAFLD) is associated with lifestyle-related diseases such as hypertension. In a previous study, we identified kininogen fragments, which are associated with hypertension, in the serum of patients with NAFLD. In this study, we examined the relationship between the pathological conditions of NAFLD and the presence of hypertension or kininogen fragments. Administration of a high-salt diet, in addition to a choline-deficient L amino-acid-defined diet, to salt-sensitive hypertensive rats revealed that hypertension aggravated hepatitis and liver fibrosis by suppressing the expression of HO-1 and IL-10, but did not affect the degree of fatty liver. On the other hand, kininogen degradation was promoted in NAFLD, but there was no association between hypertension and kininogen fragment concentration in NAFLD patients. Therefore, hypertension is an accelerating factor of NAFLD, but kininogen is not associated with the interaction between NAFLD and hypertension.

Research Products

• [Journal Article] Hypertension exacerbates liver injury and hepatic fibrosis induced by a choline-deficient L-amino acid-defined diet in rats (2014)
  • Author(s): Arima S, Uto H, Ibusuki R, Kumamoto R, Tanoue S, Mawatari S, Oda K, Numata M, Fujita H, Oketani M, Ido A, Tsubouchi H
  • Journal Title: Int J Mol Med Volume: 33(1) Pages: 68-76
  • DOI: 10.3892/ijmm.2013.1544
• [Journal Article] Increasing prevalence of diabetes mellitus in association with fatty liver in a Japanese population (2013)
  • Author(s): Imamura Y, Uto H, Hiramine Y, Hosoyamada K, Ijuin S, Yoshifuku S, Miyahara H, Maenohara S, Oketani M, Ido A, Tsubouchi H
  • Journal Title: J Gastroenterol Volume: (Epub ahead of print)
  • DOI: 10.1007/s00535-013-0902-2
• [Journal Article] Dietary fructose enhances the incidence of precancerous hepatocytes induced by administration of diethylnitrosamine in rat (2013)
  • Author(s): Kumamoto R, Uto H, Oda K, Ibusuki R, Tanoue S, Arima S, Mawatari S, Kumagai K, Numata M, Tamai T, Moriuchi A, Fujita H, Oketani M, Ido A, Tsubouchi H
  • Journal Title: Eur J Med Res Volume: 18 Pages: 54
  • DOI: 10.1186/2047-783X-18-54
• [Journal Article] Clinicopathological features of liver injury in patients with type 2 diabetes mellitus and comparative study of histologically proven nonalcoholic fatty liver diseases with or without type 2 diabetes mellitus (2013)
  • Author(s): Shima T, Uto H, Ueki K, Takamura T, Kohgo Y, Kawata S, Yasui K, Park H, Nakamura N, Nakatou T, Tanaka N, Umemura A, Mizuno M, Tanaka J, Okanoue T
  • Journal Title: J Gastroenterol Volume: 48(4) Pages: 515-25
  • DOI: 10.1007/s00535-012-0653-5
• [Journal Article] Fatty liver in men is associated with high serum levels of small, dense low-density lipoprotein cholesterol (2012)
  • Author(s): Hosoyamada K, Uto H, Imamura Y, Hiramine Y, Toyokura E, Hidaka Y, Kuwahara T, Kusano K, Saito K, Oketani M, Ido A, Tsubouchi H
  • Journal Title: Diabetol Metab Syndr Volume: 4(1) Pages: 34
• [Journal Article] Clinical and pathological progression of non-alcoholic steatohepatitis to hepatocellular carcinoma (2012)
  • Author(s): Yasui K, Hashimoto E, Tokushige K, Koike K, Shima T, Kanbara Y, Saibara T, Uto H, Takami S, Kawanaka M, Komorizono Y, Okanoue T; Japan NASH Study Group
  • Journal Title: Hepatol Res Volume: 42(8) Pages: 767-73
  • DOI: 10.1111/j.1872-034X.2012.00986.x
• [Journal Article] Characteristics of patients with nonalcoholic steatohepatitis who develop hepatocellular carcinoma (2011)
  • Author(s): Yasui K, Hashimoto E, Komorizono Y, Koike K, Arii S, Imai Y, Shima T, Kanbara Y, Saibara T, Mori T, Kawata S, Uto H, Takami S, Sumida Y, Takamura T, Kawanaka M, Okanoue T; Japan NASH Study Group, Ministry of Health, Labour, and Welfare of Japan
  • Journal Title: Clin Gastroenterol Hepatol Volume: 9(5) Pages: 428-33
  • DOI: 10.1016/j.cgh.2011.01.023
• [Journal Article] Impact of cigarette smoking on onset of nonalcoholic fatty liver disease over a 10-year period (2011)
  • Author(s): Hamabe A, Uto H, Imamura Y, Kusano K, Mawatari S, Kumagai K, Kure T, Tamai T, Moriuchi A, Sakiyama T, Oketani M, Ido A, Tsubouchi H
  • Journal Title: J Gastroenterol Volume: 46(6) Pages: 769-78
  • DOI: 10.1007/s00535-011-0376-z
• [Journal Article] Alcohol drinking patterns and the risk of fatty liver in Japanese men (2011)
  • Author(s): Hiramine Y, Imamura Y, Uto H, Koriyama C, Horiuchi M, Oketani M, Hosoyamada K, Kusano K, Ido A, Tsubouchi H
  • Journal Title: J Gastroenterol Volume: 46(4) Pages: 519-28
  • DOI: 10.1007/s00535-010-0336-z
• [Presentation] プロテオミクスから同定した非アルコール性脂肪性肝疾患の分子マーカーの臨床的意義と新しい診断 (2013)
  • Author(s): 宇都浩文、岡上武、坪内博仁
  • Organizer: 第99回日本消化器病学会総会
  • Place of Presentation: 鹿児島市
  • Year and Date: 2013-03-21
• [Presentation] Hypertension exacerbates hepatic fibrosis induced by a choline-deficient L-amino acid-defined diet in rats (2012)
  • Author(s): Arima S, Uto H, Ibusuki R, Kumamoto R, Tanoue S, Mawatari S, Kure T, Numata M, Setoyama H, Fujita H, Sakiyama T, Oketani M, Ido A, Tsubouchi H
  • Organizer: The American Gastroenterological Association (AGA)
  • Place of Presentation: Sandiego(USA)
  • Year and Date: 20120519-22
• [Presentation] 高血圧はコリン欠乏アミノ酸置換食による肝線維化を促進する (2012)
  • Author(s): 有馬志穂、宇都浩文、指宿りえ、隈元亮、熊谷公太郎、呉健、馬渡誠一、嵜山敏男、桶谷真、井戸章雄、坪内博仁
  • Organizer: 第48回日本肝臓学会総会
  • Place of Presentation: 金沢市
  • Year and Date: 2012-06-08
• [Presentation] 脂肪肝における高血圧の病態への関与 (2011)
  • Author(s): 有馬志穂、宇都浩文、隈元亮、熊谷公太郎、呉健、馬渡誠一、玉井努、森内昭博、嵜山敏男、桶谷真、井戸章雄、坪内博仁
  • Organizer: 第48回日本肝臓学会総会
  • Place of Presentation: 東京都
  • Year and Date: 2011-06-03