Analyzing PREB, the transcriptional factor, transgenic mouse for treatment of lifestyle disease

• Project/Area Number: 16K09786
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Kagawa University
• Principal Investigator: Imachi Hitomi 香川大学, 医学部, 准教授 (80380187)
• Co-Investigator(Kenkyū-buntansha): 村尾 孝児 香川大学, 医学部, 教授 (20291982)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 非アルコール性脂肪肝炎 / 生活習慣病 / PREB / ABCA1 / 脂肪肝 / アディポネクチン / 脂肪細胞 / トランスジェニックマウス / 内分泌代謝学 / 非アルコール性脂肪性肝炎 / メタボリックシンドローム / 転写因子

Outline of Final Research Achievements

Previously, we reported that the transcriptional factor, prolactin regulatory element binding (PREB) relates with lifestyle disease, such as diabetes mellitus and atherosclerosis. That is, we showed that PREB acts as anti-diabetic in pancreatic β cells and regulates adiponectin expression in adipocytes. In this study, we tried to clear the role of PREB on lifestyle disease. Results are; (1) ABCA1 is a pivotal regulator of lipid efflux from cells, and PREB increases ABCA1 expression in hepatocyte by binding to ABCA1 promoter. As a result, PREB improve fatty liver. (2) PREB regulates adiponectin expression in vivo. (3)PREB may effect protects pancreatic β cells improving lipotoxicity via ABCA expression.
Thus ABCA1 should be the target molecule of PREB, and we need to elucidate the mechanism of ABCA1 expression by PREB for lifestyle disease treatment.

Academic Significance and Societal Importance of the Research Achievements

転写因子PREBがABCA1分子発現調節を通じて細胞内脂肪蓄積やそれによる細胞機能障害により生活習慣病に関連していることが判明した。今後さらにPREBによるABCA1遺伝子の発現調節が新たな生活習慣病の治療方法に繋がると考えられる。

Research Products

• [Journal Article] Angiotensin II induces cholesterol accumulation and impairs insulin secretion by regulating ABCA1 in beta cells. (2018)
  • Author(s): Lyu J, Imachi H, Fukunaga K, Sato S, Ibata T, Kobayashi T, Dong T, Yoshimoto T, Yonezaki K, Nagata H, Iwama H, Murao K
  • Journal Title: J Lipid Res Volume: 59 Issue: 10 Pages: 1906-1915
  • DOI: 10.1194/jlr.m085886
  • Peer Reviewed
• [Journal Article] IGF1 suppresses cholesterol accumulation in the liver of growth hormone-deficient mice via the activation of ABCA1 (2018)
  • Author(s): Fukunaga Kensaku、Imachi Hitomi、Lyu Jingya、Dong Tao、Sato Seisuke、Ibata Tomohiro、Kobayashi Toshihiro、Yoshimoto Takuo、Yonezaki Kazuko、Matsunaga Toru、Murao Koji
  • Journal Title: American Journal of Physiology-Endocrinology and Metabolism Volume: 315 Issue: 6 Pages: E1232-E1241
  • DOI: 10.1152/ajpendo.00134.2018
  • Peer Reviewed / Open Access
• [Journal Article] Effect of TNF-α on the expression of ABCA1 in pancreatic β-cells (2018)
  • Author(s): Sato S, Imachi H, Lyu J, Miyai Y, Fukunaga K, Dong T, Ibata T, Kobayashi T, Yoshimoto T, Kikuchi F, Yonezaki K, Yamaji N, Iwama H, Murao K
  • Journal Title: J Mol Endocrinol Volume: 61 Issue: 4 Pages: 185-193
  • DOI: 10.1530/jme-18-0167
  • Peer Reviewed
• [Journal Article] Selective peroxisome proliferator-activated receptor-α modulator K-877 regulates the expression of ATP-binding cassette transporter A1 in pancreatic beta cells. (2018)
  • Author(s): Dong T, Lyu J, Imachi H, Kobayashi T, Fukunaga K, Sato S, Ibata T, Yoshimoto T, Yonezaki K, Iwama H, Zhang G, Murao K.
  • Journal Title: Eur J Pharmacol Volume: 838 Pages: 78-84
  • DOI: 10.1016/j.ejphar.2018.09.015
  • Peer Reviewed
• [Journal Article] Thyroid stimulating hormone stimulates the expression of glucose transporter 2 via its receptor in pancreatic β cell line, INS-1 cells. (2018)
  • Author(s): Lyu J, Imachi H, Yoshimoto T, Fukunaga K, Sato S, Ibata T, Kobayashi T, Dong T, Yonezaki K, Yamaji N, Kikuchi F, Iwama H, Ishikawa R, Haba R, Sugiyama Y, Zhang H, Murao K.
  • Journal Title: Sci Rep. Volume: 8 Issue: 1 Pages: 1986-1995
  • DOI: 10.1038/s41598-018-20449-3
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Prolactin regulatory element-binding protein is involved in suppression of the adiponectin gene in vivo (2017)
  • Author(s): Zhang XZ, Imachi H, Lyu JY, Fukunaga K, Sato S, Ibata T, Kobayashi T, Yoshimoto T, Kikuchi F, Dong T, Murao K
  • Journal Title: J Endocrinol Invest Volume: 40 Issue: 4 Pages: 437-445
  • DOI: 10.1007/s40618-016-0589-3
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Insulin-like Growth Factor 1 Regulates the Expression of ATP-Binding Cassette Transporter A1 in Pancreatic Beta Cells (2016)
  • Author(s): Lyu J, Imachi H, Iwama H, Zhang H, Murao K
  • Journal Title: Horm Metab Res Volume: 47 Issue: 05 Pages: 1-7
  • DOI: 10.1055/s-0035-1569272
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] Glucagon Expression is Regulated by Exendin-4 via CaMKK/AMPK/FoxO1 Pathway in Alpha TC1.6 Cells (2018)
  • Author(s): Lyu J, Imachi H, Fukunaga K, Sato S, Dong T, Ibata T, Kobayashi T, Murao K.
  • Organizer: American Diabetes Association 78th Scientific Session
  • Int'l Joint Research
• [Presentation] Exendin-4 suppresses cholesterol accumulation via elevation of ATP-binding cassette transporter A1 in the liver. (2018)
  • Author(s): Lyu J, Imachi H, Fukunaga K, Zhang H, Dong T, Sato S, Ibata T, Yamaji N, Yonezaki K, Kikuchi F, Yoshimoto T, Murao K.
  • Organizer: American Diabetes Association 77th Scientific Session
  • Int'l Joint Research
• [Presentation] 糖尿病の病態形成におけるHDL代謝の関与 (2016)
  • Author(s): 村尾孝児、井町仁美
  • Organizer: 第48回日本動脈硬化学会総会・学術集会
  • Place of Presentation: 東京
  • Year and Date: 2016-07-14
  • Invited