Association between the lipotoxicity of saturated fatty acids in the liver and pathophysiology of NASH.

• Project/Area Number: 25860551
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Yokohama City University
• Principal Investigator: OGAWA Yuji 横浜市立大学, 附属病院, 指導診療医 (20644959)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 非アルコール性脂肪肝疾患 / 非アルコール性脂肪肝炎 / 飽和脂肪酸 / lipotoxicity / NAFLD / NASH / パルミチン酸

Outline of Final Research Achievements

The right jugular veins of C57BL/6 mice were catheterized. Then the mice were continuously infused with ethyl palmitate. Short-term palmitate treatment recruited neutrophil and macrophage to the liver, and activated hepatic stellate cell. Long-term palmitate treatment induced liver fibrosis. We showed that the saturated fatty acid, palmitate, induces nonalcoholic steatohepatitis(NASH)-like condition. The molecular interactions in this study could provide novel therapeutic targets for the treatment of NASH.

Research Products

• [Journal Article] Simple scoring system for predicting cirrhosis in nonalcoholic fatty liver disease. (2014)
  • Author(s): Kessoku T, Ogawa Y, Yoneda M, Imajo K, Sumida Y, Eguchi Y, Fujii H, Hyogo H, Ono M, Suzuki Y, Kawaguchi T, Chayama K, Tanaka S, Fujimoto K, Anzai K, Saibara T, Sata M, Itoh Y, Nakajima A, Okanoue T
  • Journal Title: World J Gastroenterol Volume: 20（29） Issue: 29 Pages: 10108-10114
  • DOI: 10.3748/wjg.v20.i29.10108
  • Peer Reviewed / Open Access
• [Journal Article] LDL-Migration Index (LDL-MI), an Indicator of Small Dense Low-Density Lipoprotein (sdLDL), Is Higher in Non-Alcoholic Steatohepatitis than in Non-Alcoholic Fatty Liver: A Multicenter Cross-Sectional Study. (2014)
  • Author(s): Imajo K, Hyogo H, Yoneda M, Honda Y, Kessoku T, Tomeno W, Ogawa Y, Taguri M, Mawatari H, Nozaki Y, Fujita K, Kirikoshi H, Saito S, Sumida Y, Ono M, Wada K, Nakajima A
  • Journal Title: PLoS One Volume: 26 Issue: 12 Pages: e115403-e115403
  • DOI: 10.1371/journal.pone.0115403
  • Peer Reviewed / Open Access
• [Journal Article] Oral choline tolerance test as a novel noninvasive method for predicting nonalcoholic steatohepatitis. (2014)
  • Author(s): Imajo K, Yoneda M, Fujita K, Kessoku T, Tomeno W, Ogawa Y, Shinohara Y, Sekino Y, Mawatari H, Nozaki Y, Kirikoshi H, Taguri M, Toshima G, Takahashi J, Saito S, Wada K, Nakajima A.
  • Journal Title: Journal of Gastroenterology Volume: 49 Issue: 2 Pages: 295-304
  • DOI: 10.1007/s00535-013-0776-3
  • Peer Reviewed
• [Journal Article] Microbiota and nonalcoholic steatohepatitis. (2014)
  • Author(s): Imajo K, Yoneda M, Ogawa Y, Wada K, Nakajima A.
  • Journal Title: Seminars in Immunopathology Volume: 36 Issue: 1 Pages: 115-132
  • DOI: 10.1007/s00281-013-0404-6
  • Peer Reviewed
• [Journal Article] Update: epidemiology and pathophysiology of nonalcoholic fatty liver disease. (2014)
  • Author(s): Ogawa Y, Imajo K, Yoneda M, Nakajima A.
  • Journal Title: Nihon Shokakibyo Gakkai Zasshi. Volume: 111 Pages: 14-24
  • NAID: 130003383339
  • Peer Reviewed
• [Presentation] Lipotoxicity in liver induced by palmitate in vivo. 22nd United European Gastroenterology Week Free Paper Session Liver steatosis (2014)
  • Author(s): Ogawa Y, Honda Y, Kessoku T, Tomeno W, Imajo K, Mawatari H, Saito S, Nakajima A
  • Organizer: 22nd United European Gastroenterology Week
  • Place of Presentation: Vienna（Austria）
  • Year and Date: 2014-10-24 – 2014-10-28
• [Presentation] パルミチン酸単独投与による肝臓への炎症細胞浸潤についての検討 (2014)
  • Author(s): 小川祐二, 今城健人, 中島淳
  • Organizer: 2014年度日本消化器関連学会週間（JDDW 2014）
  • Place of Presentation: 神戸国際会議場（兵庫県）
  • Year and Date: 2014-10-23 – 2014-10-26
• [Presentation] パルミチン酸単独投与による肝臓への炎症細胞浸潤と線維化についての検討 (2014)
  • Author(s): 小川祐二, 本多靖, 結束貴臣, 留野渉, 今城健人, 馬渡弘典, 斉藤聡, 中島淳
  • Organizer: 第131回日本薬理学会関東部会
  • Place of Presentation: 横浜市立大学福浦キャンパス（神奈川県）
  • Year and Date: 2014-10-11
• [Presentation] パルミチン酸単独投与が引き起こす肝臓における自然免疫応答の検討 (2014)
  • Author(s): 小川祐二, 本多靖, 結束貴臣, 留野渉, 今城健人, 馬渡弘典, 斉藤聡, 中島淳
  • Organizer: 第51回日本消化器免疫学会総会
  • Place of Presentation: 京都大学医学部芝蘭会館（京都府）
  • Year and Date: 2014-07-10 – 2014-07-11
• [Presentation] パルミチン酸単独投与による肝臓における自然免疫応答についての検討 (2014)
  • Author(s): 小川祐二, 今城健人, 中島淳
  • Organizer: 第50回日本肝臓学会総会
  • Place of Presentation: ホテルニューオータニ（東京都）
  • Year and Date: 2014-05-29 – 2014-05-30
• [Presentation] Analysis of lipotoxicity in liver induced by palmitate in vivo. (2014)
  • Author(s): Ogawa Y, Honda Y, Kessoku T, Tomeno W, Imajo K, Mawatari H, Yoneda M, Kirikoshi H, Maeda S, Saito S, Wada K, Nakajima A
  • Organizer: ADDW 2014
  • Place of Presentation: Chicago（the United States of America）
  • Year and Date: 2014-05-04 – 2014-05-06
• [Presentation] 肝臓におけるパルミチン酸が引き起こすlipotoxityについてのin vivoでの検討 (2014)
  • Author(s): 小川祐二，本多靖，結束貴臣，今城健人，中島淳
  • Organizer: 第33回アルコール医学生物学研究会学術集会
  • Place of Presentation: 高知県立牧野植物園（高知）
• [Presentation] パルミチン酸単独投与による (2014)
  • Author(s): 小川 祐二，今城健人，中島 淳
  • Organizer: 第50回 肝臓病学会総会
  • Place of Presentation: ホテルニューオータニ（東京）
• [Presentation] Analysis of lipotoxicity in liver induced by palmitate in vivo. (2014)
  • Author(s): Yuji Ogawa, Takaomi Kessoku, Kento Imajo, Atsushi Nakajima
  • Organizer: Digestive Disease Week
  • Place of Presentation: Chicago（United States of America）
• [Presentation] パルミチン酸が引き起こす肝臓におけるlipotoxicityの検討 (2013)
  • Author(s): 小川 祐二，今城 健人，結束 貴臣，米田 正人，中島 淳
  • Organizer: 第10 回酸化ストレと肝研究会
  • Place of Presentation: ANAクラウンプラザホテル福岡（福岡）