The role of BAFF in hepatocarcinogenesis in diabetes, obesity and fatty liver

• Project/Area Number: 15K09007
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Ehime University
• Principal Investigator: Abe Masanori 愛媛大学, 医学系研究科, 准教授 (40432786)
• 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: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 脂肪性肝疾患 / 肝発癌 / アディポカイン / 脂肪肝 / 肥満 / 発癌

Outline of Final Research Achievements

In this study, we analyzed the role of B cell activating factor (BAFF), which is one of adipokines, in the progression of fatty liver disease, using BAFF- and BAFF-receptor (BAFF-R) knockout (KO) mice. In a high fat diet (HFD) model, insulin resistance and adipose tissue inflammation were attenuated in both BAFF- and BAFF-R KO mice. Although hepatic steatosis and hepatocarginogenesis were improved in HFD-fed BAFF-KO mice, they were enhanced in HFD-fed BAFF-R KO mice. These findings suggest that BAFF would be a key molecule of progression, including hepatocarcinogenesis, of fatty liver disease.

Research Products

• [Journal Article] Upregulated absorption of dietary palmitic acids with changes in intestinal transporters in non-alcoholic steatohepatitis (NASH) (2017)
  • Author(s): Utsunomiya H, Yamamoto Y, Takeshita E, Tokumoto Y, Tada F, Miyake T, Hirooka M, Abe M, Kumagi T, Matsuura B, Ikeda Y, Hiasa Y
  • Journal Title: J Gastroenterol Volume: 印刷中 Issue: 8 Pages: 940-954
  • DOI: 10.1007/s00535-016-1298-6
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Nonalcoholic fatty liver with a hepatic arterial buffer response strongly associated with future metabolic disease. (2017)
  • Author(s): Hirooka M, Koizumi Y, Miyake T, Watanabe T, Yoshida O, Tokumoto Y, Yukimoto A, Nakamura Y, Imai Y, Abe M, Hiasa Y.
  • Journal Title: Hepatol Commun. Volume: 1 Issue: 7 Pages: 623-633
  • DOI: 10.1002/hep4.1070
  • Peer Reviewed / Open Access
• [Journal Article] Quantitative assessment of liver fibrosis reveals a nonlinear association with fibrosis stage in nonalcoholic fatty liver disease. (2017)
  • Author(s): Masugi Y, Abe T, Tsujikawa H, Effendi K, Hashiguchi A, Abe M, Imai Y, Hino K, Hige S, Kawanaka M, Yamada G, Kage M, Korenaga M, Hiasa Y, Mizokami M, Sakamoto M
  • Journal Title: Hepatol Commun Volume: 27 Issue: 1 Pages: 58-68
  • DOI: 10.1002/hep4.1121
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Differences in the risk of fatty liver for onset of impaired fasting glucose according to baseline plasma glucose levels (2017)
  • Author(s): Miyake T, Hirooka M, Yoshida O, Furukawa S, Kumagi T, Koizumi M, Yamamoto S, Kuroda T, Arimitsu E, Takeshita E, Abe M, Kitai K, Matsuura B, Hiasa Y
  • Journal Title: J Gastroenterol Volume: 52 Issue: 2 Pages: 237-244
  • DOI: 10.1007/s00535-016-1234-9
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Interleukin-34 as a fibroblast-derived marker of liver fibrosis in patients with non-alcoholic fatty liver disease. (2016)
  • Author(s): Shoji H, Yoshio S, Mano Y, Kumagai E, Sugiyama M, Korenaga M, Arai T, Itokawa N, Atsukawa M, Aikata H, Hyogo H, Chayama K, Ohashi T, Ito K, Yoneda M, Nozaki Y, Kawaguchi T, Torimura T, Abe M, Hiasa Y, Kamiyama T, Fukai M, Taketomi A, Mizokami M, Kanto T*
  • Journal Title: Scientific Reports Volume: 6:28814 Issue: 1 Pages: 1-10
  • DOI: 10.1038/srep28814
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Low alcohol consumption increases the risk of impaired glucose tolerance in patients with non-alcoholic fatty liver disease. (2016)
  • Author(s): Teruki Miyake
  • Journal Title: Journal of Gastroenterology Volume: 印刷中 Issue: 11 Pages: 1090-1100
  • DOI: 10.1007/s00535-016-1194-0
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Characterization of Liver Monocytic Myeloid-Derived Suppressor Cells and Their Role in a Murine Model of Non-Alcoholic Fatty Liver Disease (2016)
  • Author(s): Yao L, Abe M, Kawasaki K, Akbar SM, Matsuura B, Onji M, Hiasa Y.
  • Journal Title: PLoS One Volume: 11 Issue: 2 Pages: e0149948-e0149948
  • DOI: 10.1371/journal.pone.0149948
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Association between Wisteria floribunda agglutinin-positive Mac-2 binding protein and the fibrosis stage of non-alcoholic fatty liver disease (2015)
  • Author(s): Abe M, Miyake T, Kuno A, Imai Y, Sawai Y, Hino K, Hara Y, Hige S, Sakamoto M, Yamada G, Kage M, Korenaga M, Hiasa Y, Mizokami M, Narimatsu H
  • Journal Title: J Gastroenterol Volume: 50 Issue: 7 Pages: 776-784
  • DOI: 10.1007/s00535-014-1007-2
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Increased frequency of myeloid-derived suppressor cells in patients with non-alcoholic fatty liver disease (2017)
  • Author(s): Abe M, Nakamura Y, Miyake T, Yukimoto A, Imai Y, Watanabe T, Yoshida O, Hirooka M, Hiasa Y
  • Organizer: AASLD Liver Meeting 2017
  • Int'l Joint Research
• [Presentation] Accumulation of monocytic myeloid-derived suppressor cells in the liver of a murine model of non-alcoholic fatty liver disease (2016)
  • Author(s): Abe M, Lao Y, Nakamura Y, Miyake T, Imai Y, Qatanabe T, Koizumi Y, Yoshida O, Tokumoto Y, Hirooka M, Kumagi T, Hiasa Y
  • Organizer: The Liver Meeting 2016
  • Place of Presentation: ボストン
  • Year and Date: 2016-11-11
  • Int'l Joint Research
• [Presentation] NAFLDマウスモデル肝臓における骨髄由来抑制細胞の増加機序の解析 (2016)
  • Author(s): 阿部雅則、姚立穎、中村由子、吉田理、三宅映己、今井祐輔、渡辺崇夫、徳本良雄、廣岡昌史、日浅陽一
  • Organizer: 第20回日本肝臓学会総会
  • Place of Presentation: 神戸市
  • Year and Date: 2016-11-03
• [Presentation] 肝臓に局在する単球系骨髄由来抑制細胞の同定と免疫抑制機序の解析 (2016)
  • Author(s): 阿部雅則、姚立穎、中村由子、今井祐輔、渡辺崇夫、吉田理、小泉洋平、徳本良雄、廣岡昌史、日浅陽一
  • Organizer: 第52回日本肝臓学会総会
  • Place of Presentation: 千葉市
  • Year and Date: 2016-05-19
• [Presentation] Characterization of liver myeloid-derived suppressor cells in nonalcoholic fatty liver disease (2016)
  • Author(s): Abe M, Yao L, Nakamura Y, Imai Y, Watanabe T, Yoshida O, Tokumoto Y, Abe M, Hiasa Y
  • Organizer: 25th Conference of the Asian Pacific Association for the Study of the Liver
  • Place of Presentation: 東京都港区
  • Year and Date: 2016-02-20
  • Int'l Joint Research
• [Presentation] Identification of liver monocytic myeloid-derived suppressor cells and elucidation of their roles in non-alcoholic fatty liver disease (2015)
  • Author(s): Yao L, Abe M, Miyake T, Nakamura Y, Imai Y, Koizumi Y, Watanabe T, Yoshida O, Hirooka M, Tokumoto Y, Matsuura B, Hiasa Y
  • Organizer: The Liver Meeting 2015
  • Place of Presentation: San Fransisco, USA
  • Year and Date: 2015-11-13
  • Int'l Joint Research
• [Presentation] NAFLDにおける新規糖鎖マーカーWFA+-M2BPによる肝線維化進展性の抽出 (2015)
  • Author(s): 阿部雅則、三宅映己、今井康陽、澤井良之、日野啓輔、原裕一、坂元亨宇、山田剛太郎、鹿毛政義、日浅陽一、是永匡紹、溝上雅史、久野敦、成松久
  • Organizer: 第2回肝臓と糖尿病・代謝研究会
  • Place of Presentation: 山口県下関市
  • Year and Date: 2015-05-23