The roles of CREBH in non-alcoholic fatty liver

• Project/Area Number: 26500001
• 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 Tsukuba
• Principal Investigator: KOBAYASHI Kazuto 筑波大学, 医学医療系, 研究員 (30455935)
• Co-Investigator(Kenkyū-buntansha): 中川 嘉 筑波大学, 国際統合睡眠医科学研究機構, 准教授 (80361351)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 非アルコール性脂肪肝 / 脂質代謝 / 生活習慣病 / 遺伝子発現

Outline of Final Research Achievements

In this study, we examined how CREBH is involved in lifestyle-related diseases, especially on the development and progression of nonalcoholic fatty liver. CREBH liver-specific KO (LKO) mouse using CRISPR/Cas9 system was successfully produced. The mouse exhibited a remarkable increase in blood lipids upon fasting. One of the causes is the increase of the transcription factor SREBPs which govern the expression of fatty acid and cholesterol synthesis genes. When LKO mice were fed with methionine choline deficient diet, which is a nonalcoholic fatty liver model, severe liver injury appeared in the early period. In this study, we have established a method for preparing new genetically modified mice, and clarified that deficiency of CREBH induces nonalcoholic fatty liver.

Research Products

• [Journal Article] Hyperlipidemia and hepatitis in liver-specific CREB3L3 knockout mice generated using a one-step CRISPR/Cas9 system. (2016)
  • Author(s): Nakagawa Y, Oikawa F, Ohno H, Yagishita Y, Satoh A, Osaki Y, Takei K, Kikuchi T, Song-iee H, Mizuno S. Matsuzaka T, Iwasaki H, Kobayashi K, Yatoh S, Yahagi N, Suzuki H, Sone H, Takahashi S, Yamada N, Shimano H.
  • Journal Title: Sci Rep. Volume: 6 Issue: 1 Pages: 27857-27857
  • DOI: 10.1038/srep27857
  • NAID: 120007135376
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Remarks] 筑波大学 医学医療系 内分泌代謝・糖尿病内科
  • URL: http://www.u-tsukuba-endocrinology.jp/