Elucidation of the relationship between polyamine synthesis and fatty acid synthesis in obesity formation and the investigation of drug targets

• Project/Area Number: 17K16156
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Metabolomics
• Research Institution: Jikei University School of Medicine
• Principal Investigator: TAJIMA AYASA 東京慈恵会医科大学, 医学部, 助教 (20780688)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: ポリアミン / アンチザイム / ATPクエン酸リアーゼ / 肥満 / 脂質代謝 / 脂肪酸 / 3T3-L1 / 脂質

Outline of Final Research Achievements

ATP citrate lyase (ACLY) is an acetyl-CoA synthase and is involved in fatty acid synthesis. Previous studies have demonstrated that the polyamine regulator antizyme (AZ) binds ACLY to enhance activity and increase acetyl-CoA production. In this study, I investigated the effect of ACLY on the polyamine metabolism system and investigated its interaction with the fatty acid metabolism. It was found that ACLY is not only used in the fatty acid synthesis system, but it is also consumed in the acetylation of polyamine. This suggests that both metabolic systems are closely related.

Academic Significance and Societal Importance of the Research Achievements

日本人の肥満者(BMI≧25)の割合は、男性 30.7%、女性 21.9% (平成30年度国民健康・栄養調査結果)とされ、肥満は糖尿病・高血圧・脂質異常症と同様に、改善を必要とする生活習慣病であり、効果的な抑制策が必要とされている。そのため、肥満メカニズムの解明は重要であり、本研究により明らかとなった新たな機能から、ACLYを分子標的とする脂肪酸合成系とポリアミン代謝系の両方に影響を及ぼす物質の検索をすることで、今後の肥満の予防法・治療法への応用が期待される。

Research Products

• [Journal Article] Investigation of the effects of urea cycle amino acids on the expression of ALB and CEBPB in the human hepatocellular carcinoma cell line FLC-4 (2020)
  • Author(s): Takahiko J. Fujimi, Yoshihiro Mezaki, Takahiro Masaki, Ayasa Tajima, Mariko Nakamura, Akira Yoshikawa, Noriyuki Murai, Mamoru Aizawa, Soichi Kojima, Yoshihiro Matsumoto, Hideki Aizaki, Tomokazu Matsuura,
  • Journal Title: Human Cell Volume: -
  • Peer Reviewed
• [Journal Article] Novel ubiquitin-independent nucleolar c-Myc degradation pathway mediated by antizyme 2 (2018)
  • Author(s): Murai Noriyuki、Murakami Yasuko、Tajima Ayasa、Matsufuji Senya
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 3005-3005
  • DOI: 10.1038/s41598-018-21189-0
  • Peer Reviewed / Open Access
• [Presentation] Antizyme and ATP citrate lyase suppresses the cell death of ornithine decarboxylase-overproducing cell line (2018)
  • Author(s): Ayasa Tajima
  • Organizer: 5th International Conference on Polyamines: Biochemical, Physiological and Clinical Perspectives
  • Int'l Joint Research
• [Presentation] Relationship between ATP citrate lyase and Polyamine metabolism (2017)
  • Author(s): Ayasa Tajima
  • Organizer: Gordon Research Conference
  • Int'l Joint Research