Growth promoting mechanism by fatty acids

• Project/Area Number: 18K06246
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 44020:Developmental biology-related
• Research Institution: The University of Tokyo
• Principal Investigator: Fukuyama Masamitsu 東京大学, 大学院薬学系研究科(薬学部), 講師 (20422389)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 線虫 / 栄養 / 脂肪酸 / 必須アミノ酸 / 成長 / 脂質 / 分子遺伝学 / アミノ酸 / 栄養応答 / 個体成長

Outline of Final Research Achievements

Nutrients are the most proximal factors that promote animals growth. However, the mechanism by which they confer the effect remains largely uncovered. We have shown that combination of ethanol, or fatty acids and essential amino acids trigger initiation of larval growth in C. elegans. We found that hhat-2 gene suppresses larval growth by suppressing expression of lipid biosynthesis genes and accumulation of lipid dropolets. hhat-2 is exclusively expressed in neuronal cells. These findings suggest that the nervous system regulates animal growth by regulating lipid metabolism via hhat-2.

Academic Significance and Societal Importance of the Research Achievements

成長期での適切な食事が健全な成長に重要であることは周知の事実であるが、その生物学的なメカニズムは不明な点が多く残されている。例えば、食事中のどの栄養成分が、どのように成長を促進するか、遺伝子や細胞の解像度では詳細な記述が不十分であり、詳しく理解されていないのが現状である。我々は、個体の一生の成長過程を１細胞の解像度で追跡可能であるC. elegansという線虫をもちい、食事中のどの栄養素が、どの遺伝子を介して成長を制御しているかを研究してきた。本研究では、神経系でhhat-2という遺伝子がはたらき、脂質の代謝を制御することで、個体の成長を制御する可能性を見出した。

Research Products

• [Int'l Joint Research] バーゼル大学(スイス)
• [Int'l Joint Research] バーゼル大学(スイス)
• [Int'l Joint Research] バーゼル大学(スイス)
• [Journal Article] Patched regulates lipid homeostasis by controlling cellular cholesterol levels (2021)
  • Author(s): Cadena del Castillo Carla E.、Hannich J. Thomas、Kaech Andres、Chiyoda Hirohisa、Brewer Jonathan、Fukuyama Masamitsu、Faergeman Nils J.、Riezman Howard、Spang Anne
  • Journal Title: Nature Communications Volume: 12 Issue: 1 Pages: 1-1
  • DOI: 10.1038/s41467-021-24995-9
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Caenorhabditis elegans PTR/PTCHD PTR-18 promotes the clearance of extracellular hedgehog-related protein via endocytosis (2021)
  • Author(s): Chiyoda Hirohisa、Kume Masahiko、del Castillo Carla Cadena、Kontani Kenji、Spang Anne、Katada Toshiaki、Fukuyama Masamitsu
  • Journal Title: PLOS Genetics Volume: 17 Issue: 4 Pages: e1009457-e1009457
  • DOI: 10.1371/journal.pgen.1009457
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Caenorhabditis elegans PTR/PTCHD PTR-18 promotes the clearance of extracellular hedgehog-related protein via endocytosis (2021)
  • Author(s): Hirohisa Chiyoda, Masahiko Kume, Carla Cadena del Castillo, Kenji Kontani, Anne Spang, Toshiaki Katada, Masamitsu Fukuyama
  • Journal Title: Plos Genetics Volume: 17
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Hedgehog-related Genes Regulate Reactivation of Quiescent Neural Progenitors in Caenorhabditis Elegans (2019)
  • Author(s): Masahiko Kume , Hirohisa Chiyoda , Kenji Kontani, Toshiaki Katada, Masamitsu Fukuyama
  • Journal Title: Biochem Biophys Res Commun . Volume: 520 Issue: 3 Pages: 532-537
  • DOI: 10.1016/j.bbrc.2019.10.045
  • Peer Reviewed
• [Presentation] 必須アミノ酸欠乏を検知し前駆細胞の活性化を抑制する遺伝学的経路の解明 (2020)
  • Author(s): Masamitsu Fukuyama & Toshiaki Katada
  • Organizer: 第43回日本分子生物学会オンライン年会
  • Invited
• [Presentation] 必須アミノ酸欠乏センシング機構と その恒常性維持機能の解明 (2020)
  • Author(s): 福山 征光
  • Organizer: 第８回AAA(Academy of Aging and Cardinovascular-Diabetes Research)研究会
  • Invited
• [Presentation] 個体成長と老化を司る栄養応答機構の分子遺伝学的解析 (2019)
  • Author(s): 福山 征光、千代田 大尚、堅田 利明
  • Organizer: 群馬大学生体調節研究所 第５回内分泌代謝シンポジウム
  • Invited
• [Presentation] 必須アミノ酸欠乏を検知し線虫の個体成長を停止する遺伝学的経路の解明 (2019)
  • Author(s): 福山 征光、堅田 利明
  • Organizer: 第９２回日本生化学会大会 シンポジウム
  • Invited
• [Presentation] Dietary nutrients and genes that regulate growth in C. elegans. (2019)
  • Author(s): Fukuyama M. & Katada T.
  • Organizer: The 9th Federation of the Asian and Oceanian Physiological Society Congress (FAOPS2019)
  • Invited
• [Presentation] ptr-18/PTCHD maintains quiescence of neural progenitor cells during L1 diapause by suppressing the activity of grl-7 through endocytosis. (2019)
  • Author(s): Chiyoda, H., Kume, M., Katada, T., Fukuyama, M
  • Organizer: 22nd International C. elegans Meeting
  • Int'l Joint Research
• [Presentation] Nutritional regulation of C. elegans development (2019)
  • Author(s): Fukuyama M
  • Organizer: The 9th Federation of the Asian and Oceanian Physiological Society Congress
  • Int'l Joint Research / Invited
• [Presentation] 線虫の栄養による休眠制御機構の研究 (2018)
  • Author(s): 福山 征光
  • Organizer: ExCELLS研究会「休眠と代謝研究会」
  • Invited
• [Book] Reproductive and Developmental Strategies (2018)
  • Author(s): Fukuyama, M
  • Total Pages: 32
  • Publisher: Springer Japan
  • ISBN: 9784431566090
• [Remarks] 東京大学大学院薬学系研究科生理化学教室
  • URL: http://www.f.u-tokyo.ac.jp/~seiri/