Role of lipotoxity in NASH

• Project/Area Number: 25293175
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Yokohama City University
• Principal Investigator: NAKAJIMA Atsushi 横浜市立大学, 医学(系)研究科(研究院), 教授 (30326037)
• Co-Investigator(Kenkyū-buntansha): SAITO Satoru 横浜市立大学, 医学部, 准教授 (00275041) ; IMAJO Kento 横浜市立大学, 附属病院, 助教 (30600192) ; YONEDA Masato 横浜市立大学, 附属病院, 講師 (10423831)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000); Fiscal Year 2015: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2013: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
• Keywords: 脂肪肝 / NASH / NAFLD / 非アルコール性脂肪肝炎 / 脂質毒性 / 慢性肝炎 / 脂肪肝炎 / lipotoxicity / 脂肪酸

Outline of Final Research Achievements

Non Alcoholic Steato-hepatitis (NASH)is a emerging disease which arise from Non Alcoholic Fatty Liver(NAFLD). The number of NAFLD patient is estimated about 20 million in Japan. NASH is the highest number of patients among liver disease. In this study, we investigate the effect of free fatty acid, palmitate on mouse liver. Administration of free fatty acid induced the inflammatory cells infiltration and activate stellate cells and fibrosis formation in the liver. We showed the neutrophil infiltration is caused by the production of the chemokine by the free fatty acids whereas fibrosis directly induced by free fatty acids via TLR4.

Research Products

• [Journal Article] The Selective SGLT2 Inhibitor Ipragliflozin Has a Therapeutic Effect on Nonalcoholic Steatohepatitis in Mice. (2016)
  • Author(s): Honda Y, Imajo K, Kato T, et al.
  • Journal Title: PLoS One Volume: 11 Issue: 1 Pages: e0146337-e0146337
  • DOI: 10.1371/journal.pone.0146337
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Magnetic Resonance Imaging More Accurately Classifies Steatosis and Fibrosis in Nonalcoholic Fatty Liver Disease Than Transient Elastography. (2016)
  • Author(s): Imajo K, Kessoku T, Honda Y, Tomeno W, Ogawa Y, Mawatari H, Fujita K, Yoneda M, Taguri M, Hyogo H, Sumida Y, Ono M, Eguchi Y, Inoue T,Yamanaka T, Wada K, Saito S, Nakajima A
  • Journal Title: Gastroenterology Volume: 150 Issue: 3 Pages: 626-37
  • DOI: 10.1053/j.gastro.2015.11.048
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Resveratrol ameliorates fibrosis and inflammation in a mouse model of nonalcoholic steatohepatitis. (2016)
  • Author(s): Kessoku T, Imajo K, Honda Y, et al.
  • Journal Title: Sci Rep Volume: 25 Issue: 1 Pages: 22251-22251
  • DOI: 10.1038/srep22251
  • NAID: 120005749754
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [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] Soluble CD14 levels reflect liver inflammation in patients with nonalcoholic steatohepatitis. (2013)
  • Author(s): Ogawa Y, Imajo K, Yoneda M, Kessoku T, Tomeno W, Shinohara Y, Kato S, Mawatari H, Nozaki Y, Fujita K, Kirikoshi H, Maeda S, Saito S, Wada K, Nakajima A.
  • Journal Title: PLoS One Volume: 8(6) Issue: 6 Pages: 65211-65211
  • DOI: 10.1371/journal.pone.0065211
  • Peer Reviewed
• [Presentation] パルミチン酸単独投与による自然免疫応答を介した肝線維化についての検討 (2015)
  • Author(s): 小川 祐二、本多靖、結束貴臣、留野渉、今城健人、馬渡弘典、藤田浩司、斉藤聡、中島淳
  • Organizer: 第51回日本肝臓学会総会
  • Place of Presentation: ホテル日航熊本・熊本ホテルキャッスル・鶴屋東館（鶴屋ホール・くまもと県民交流館パレア）・同仁堂（熊本）
  • Year and Date: 2015-05-21