Investigation of pathogenic mechanism of non-alcoholic steatohepatitis and nutritional treatment based on the mechanism

• Project/Area Number: 24614011
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Integrated Nutrition Science
• Research Institution: University of Nagasaki
• Principal Investigator: OMAGARI Katsuhisa 長崎県立大学, 看護栄養学部, 教授 (90244045)
• Research Collaborator: ICHIMURA Mayuko 長崎県立大学, 人間健康科学研究科 ; HATANAKA Maiko 長崎県立大学, 人間健康科学研究科 ; KATO Shigeko 元・長崎県立大学, 看護栄養学部, 助教 ; TSUNEYAMA Koichi 元・富山大学, 医学部, 准教授 ; GOTO Shiho ; SAKAMOTO Ai ; TORII Haruna ; HATTORI Miki ; KAWASE Miku ; MASUZUMI Miki ; SAKAKI Mika ; INOUE Shin-ichi ; TANAKA Yuna ; MURAYAMA Toshie ; YOSHIKAWA Chisato
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 非アルコール性脂肪性肝障害 / 食餌性コレステロール / 肝線維化 / 非アルコール性脂肪性肝炎 / 高コレステロール食 / SDラット / フィコシアニン / 内皮型一酸化窒素合成酵素 / アディポネクチン

Outline of Final Research Achievements

Nine-week-old male SHR/NDmcr-cp rats and Sprague–Dawley (SD) rats were fed with high-fat and high-cholesterol (HFC) diets for 9 weeks. At 18 weeks of age, rats developed non-alcoholic steatohepatitis (NASH) with advanced hepatic fibrosis. In contrast, SD rats fed with high-fat without high-cholesterol diets did not develop NASH and fibrosis. This may indicate that dietary cholesterol induces hepatic features of NASH and eventually progressed cirrhosis in rats within 9 weeks. Phycocyanin is a pigment found in the blue-green algae, Spirulina, which possesses anti-oxidative and anti-inflammatory effects. SD rats fed an HFC diet with phycocyanin did not reveal an obvious histopathological improvement, whereas serum transaminases levels tended to decrease in a dose-dependent manner.

Research Products

• [Journal Article] An SHR/NDmcr-cp rat model of non-alcoholic steatohepatitis with advanced librosis induced by a high-fat, high-cholesterol diet (2015)
  • Author(s): Ichimura M, Hatanaka M, Tsuneyama K, Kato S, Omagari K
  • Journal Title: Journal of Obesity & Weight Loss Therapy Volume: 5 Issue: 01 Pages: 244-244
  • DOI: 10.4172/2165-7904.1000244
  • Peer Reviewed / Open Access
• [Journal Article] I Iigh-fat and high-cholesterol diet rapidly induces non-alcoholic steatohepatitis with advanced fibrosis in Sprague-Dawley rats (2015)
  • Author(s): Ichimura M, Kawase M, Masuzumi M, Sakaki, Nagata Y, Tanaka K, Suruga K, Tamaru S, Kato S, Tsuneyama K, Omagari K
  • Journal Title: Hepatolgy Research Volume: 45 Issue: 4 Pages: 458-469
  • DOI: 10.1111/hepr.12358
  • Peer Reviewed / Open Access
• [Journal Article] Abdominal subcutaneous adipose tissue accumulation is positively correlated with hepatic steatosis in Sprague-Dawley rats. (2014)
  • Author(s): Katsuhisa Omagari, Chisato Yoshikawa, Shin-ichi Inoue, Yuna Tanaka, Toshie Murayama, Mayuko Ichimura, Ayako Miyata, Sawako Mori, Mai Kamogawa, Eri Hirao, Shigeko Kato, Kazuhito Suruga, Koichi Tsuneyama
  • Journal Title: Acta Medica Nagasakiensia Volume: 59 Pages: 47-56
  • NAID: 110009959615
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Phycocyanin prevents hypertension and low serum adiponectin level in a rat model of metabolic syndrome (2013)
  • Author(s): Ichimura M, Kato S, Tsuneyama K, et al.
  • Journal Title: Nutr Res. Volume: (In press) Issue: 5 Pages: 397-405
  • DOI: 10.1016/j.nutres.2013.03.006
  • Peer Reviewed
• [Presentation] SDラットにおける高脂肪・高コレステロール食によるNASH肝硬変モデルの作成 (2014)
  • Author(s): 市村真祐子、常山幸一、大曲勝久
  • Organizer: 第18回日本肝臓学会大会
  • Place of Presentation: 神戸国際会議場（兵庫県・神戸市）
  • Year and Date: 2014-10-23
• [Presentation] High-fat and high-cholesterol diet rapidly induces nonalcoholic steatohepatitis with advanced fibrosis in Sprague-Dawley rats (2014)
  • Author(s): Ichimura M, Kawase M, Masuzumi M, Sakaki M, Nagata Y, Tanaka K, Suruga K, Tsuneyama K, Omagari K.
  • Organizer: 23rd conference of the Asian Pacific Association for the Study of the Liver
  • Place of Presentation: Brisbane Convention & Exhibition Centre （オーストラリア・ブリスベーン）
• [Presentation] 高コレステロール・高脂肪食による高度線維化を伴うNASH動物モデルの作成 (2013)
  • Author(s): 市村真祐子、畑中麻衣子、常山幸一、加藤滋子、大曲勝久
  • Organizer: 第67回日本栄養・食糧学会大会
  • Place of Presentation: 名古屋大学東山キャンパス豊田講堂（名古屋）
• [Presentation] Phycocyanin prevents hypertension through improving vascular dysfunction (2013)
  • Author(s): Ichimura M, Hatanaka M, Ito MK, Omagari K.
  • Organizer: The 8th Japan-Korea International Nursing Conference
  • Place of Presentation: 長崎県立大学シーボルト校（長崎県西彼杵郡長与町）
• [Presentation] 高コレステロール・高脂肪食による高度線維化を伴うNASH動物モデルの作成 (2013)
  • Author(s): 市村真祐子、畑中麻衣子、常山幸一、加藤滋子、大曲勝久
  • Organizer: 第67回日本栄養・食糧学会大会
  • Place of Presentation: 名古屋大学
• [Remarks] 長崎県立大学ホームページ・研究情報詳細
  • URL: http://sun.ac.jp/research/researcher/researcher_detail/?uid=omagari
• [Remarks] 大曲研究室ホームページ
  • URL: http://sun.ac.jp/prof/omagari/