Elucidation of regulatory mechanism in musculoskeletal homeostasis by middle-chain fatty acylated proteins.

2022 Fiscal Year Final Research Report

• Project/Area Number: 20H04107
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: Kumamoto University
• Principal Investigator: Yoshizawa Tatsuya 熊本大学, 大学院生命科学研究部(医), 准教授 (40313530)
• Co-Investigator(Kenkyū-buntansha): 小野 悠介 熊本大学, 発生医学研究所, 教授 (60601119)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 運動器 / 骨 / 骨格筋 / アシル化 / サーチュイン

Outline of Final Research Achievements

We aim to elucidate the importance of middle-chain fatty acylated proteins in the regulatory mechanism of metabolic homeostasis. As a results, we revealed that SIRT7, which is the member of sirtuins　(SIRT1-7 in mammals) regulating a wide variety of biological process, can catalyze lysine-middle-chain fatty acylation strongly, and found novel lysine-decanoylated proteins. Furthermore, we discovered that SIRT7 can regulate lipogenesis in white adipose tissue, thermogenesis and energy metabolism in brown adipose tissue, aging, and skeletal muscle regeneration.

Free Research Field

代謝

Academic Significance and Societal Importance of the Research Achievements

リジン残基が中長鎖脂肪酸アシル化されるタンパク質自体は僅かしか報告されておらず、世界初の中鎖脂肪酸修飾タンパク質の発見などは多くの生命現象に関わる研究であり、非常に大きな意義と新規性・独自性の高い研究といえる。我々の研究成果は、運動器疾患や内分泌代謝異常症において、リジン中鎖脂肪酸アシル化修飾の調節が新規の薬剤開発の標的になる可能性を世界に先駆けて示すことができる。