Elucidation of rhythm formation mechanism and treatment strategies of thermogenesis in brown adipocytes

• Project/Area Number: 18K08470
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Kanazawa University
• Principal Investigator: Ando Hitoshi 金沢大学, 医学系, 教授 (50382875)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 肥満 / 生活習慣病 / 生体リズム / 体内時計 / 時計遺伝子 / 褐色脂肪細胞 / 熱産生

Outline of Final Research Achievements

To elucidate the pathophysiological role of circadian clock in brown adipocytes (BA), BA-specific clock knockout mice were generated. This strain showed impairment of thermogenesis using fatty acids and maintained body temperature by increasing shivering and behavioral thermogenesis. Moreover, the conditional knockout mice exhibited reduced energy expenditure and were more prone to diet-induced obesity. These results reveal the importance of the BA clock for controlling thermogenesis and preventing/treating obesity and related diseases.

Academic Significance and Societal Importance of the Research Achievements

これまでの様々な研究により、不規則な生活が肥満をもたらすことは明らかにされていたが、その機序は十分にはわかっていなかった。本研究はBAの体内時計は熱産生の制御に重要であり、そのため、BAの体内時計障害は肥満の一因になることを明らかにした。本研究の成果は、24時間社会で不規則な生活を送らざるを得ない人々に対する新しい肥満、生活習慣病の予防・治療法の開発につながることが期待される。

Research Products

• [Journal Article] Brown adipocyte-specific knockout of Bmal1 causes mild but significant thermogenesis impairment in mice (2021)
  • Author(s): Hasan Nazmul、Nagata Naoto、Morishige Jun-ichi、Islam Md Tarikul、Jing Zheng、Harada Ken-ichi、Mieda Michihiro、Ono Masanori、Fujiwara Hiroshi、Daikoku Takiko、Fujiwara Tomoko、Maida Yoshiko、Ota Tsuguhito、Shimba Shigeki、Kaneko Shuichi、Fujimura Akio、Ando Hitoshi
  • Journal Title: Molecular Metabolism Volume: 49 Pages: 101202-101202
  • DOI: 10.1016/j.molmet.2021.101202
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Elucidation of pathophysiology and treatment strategies of peripheral clock disruption (2018)
  • Author(s): 安藤 仁
  • Journal Title: 金沢大学十全医学会雑誌 Volume: 127 Issue: 3 Pages: 108-109
  • DOI: 10.24517/00053875
  • NAID: 120006605150
  • URL: https://kanazawa-u.repo.nii.ac.jp/records/47551
• [Presentation] Effect of brown adipocyte-specific Bmal1 knockout on thermogenic rhythm in mice (2020)
  • Author(s): Nazmul Hasan、長田直人、盛重純一、太田嗣人、榛葉繁紀、藤村昭夫、安藤 仁
  • Organizer: 第93回日本内分泌学会学術総会
• [Presentation] Brown adipocyte-specific knockout of Bmal1 has a significant effect on thermogenesis in mice (2020)
  • Author(s): Nazmul Hasan, Naoto Nagata, Jun-ichi Morishige, Md Tarikul Islam, Michihiro Mieda, Tsuguhito Ota, Shigeki Shimba, Akio Fujimura, Hitoshi Ando
  • Organizer: 第27回日本時間生物学会学術大会
• [Presentation] 生活習慣病における末梢体内時計の病態生理学的意義の解明 (2020)
  • Author(s): 安藤 仁
  • Organizer: 第41回日本臨床薬理学会学術総会
• [Presentation] 時間治療の現状と打開策 (2019)
  • Author(s): 安藤 仁
  • Organizer: 第26回日本時間生物学会学術大会
• [Remarks] 体内時計の障害が肥満をもたらすメカニズムの一端を解明
  • URL: https://www.kanazawa-u.ac.jp/wp-content/uploads/2021/03/210315-1.pdf
• [Remarks] 体内時計の障害が肥満をもたらすメカニズムの一端を解明
  • URL: https://www.kanazawa-u.ac.jp/rd/91090