The potential role of melanopsin in metabolic regulation

• Project/Area Number: 18K06316
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 44040:Morphology and anatomical structure-related
• Research Institution: Hokkaido University (2020); Keio University (2018-2019)
• Principal Investigator: SON YOULEE 北海道大学, 遺伝子病制御研究所, 講師 (10605306)
• 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: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: メラノプシン (Opn4) / 概日時計 / 代謝 / 脂肪 / メラノプシン（Opn4） / 摂食 / メラノプシン / メラノプシン発現網膜神経節細胞 / 非視覚光応答 / 肥満 / 脂肪細胞 / メラノプシン/Opn4 / 代謝異常

Outline of Final Research Achievements

The circadian clock has an internally driven 24-hour rhythm. Circadian rhythms generated by central and peripheral clocks maintain homeostasis, including the regulation of metabolic processes. It has been well described that disorders of circadian rhythm promote systemic metabolic dysfunction associated with obesity or diabetes. Melanopsin photopigment expressed in intrinsically photosensitive retinal ganglion cells plays a crucial role in the circadian photoentrainment through the direct projection of melanopsin-expressing cells to the master clock located in the suprachiasmatic nuclei. Thus, disruption of the melanopsin gene impairs circadian photoentrainment, which may lead to metabolic dysfunction. To understand the involvement of melanopsin in metabolic regulation, I examined the phenotype of melanopsin-disrupting mice and measured several risk factors for obesity and metabolic syndrome, such as glucose/insulin tolerance and plasma free fatty acid levels.

Academic Significance and Societal Importance of the Research Achievements

代謝異常から起こる網膜機能障害についてはよく知られているが、網膜機能障害が代謝異常を引き起こす原因になる可能性についてはほとんど検討されていない。また、非視覚応答は重要な生理的機能を果たしているにも関わらず、非視覚応答に関する研究は、視覚応答と比べて大幅に遅れていた。メラノプシンの遺伝子破壊マウスのさまざまな代謝状態を解析した本研究により、メラノプシンによる非視覚応答システムの機能障害は代謝異常をもたらす可能性が示唆され、代謝病態制御の理解に対する新たな視点を提示することになると期待される。

Research Products

• [Int'l Joint Research] University of Edinburgh/Roslin Institute(英国)
• [Int'l Joint Research] University of Southern California(米国)
• [Int'l Joint Research] University of Edinburgh(英国)
• [Journal Article] Isoform-selective regulation of mammalian cryptochromes (2020)
  • Author(s): Miller Simon、Son You Lee、Aikawa Yoshiki、Makino Eri、Nagai Yoshiko、Srivastava Ashutosh、Oshima Tsuyoshi、Sugiyama Akiko、Hara Aya、Abe Kazuhiro、Hirata Kunio、Oishi Shinya、Hagihara Shinya、Sato Ayato、Tama Florence、Itami Kenichiro、Kay Steve A.、Hatori Megumi、Hirota Tsuyoshi
  • Journal Title: Nature Chemical Biology Volume: - Issue: 6 Pages: 676-685
  • DOI: 10.1038/s41589-020-0505-1
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Molecular Mechanisms of Gonadotropin-Inhibitory Hormone (GnIH) Actions in Target Cells and Regulation of GnIH Expression (2019)
  • Author(s): Son You Lee、Ubuka Takayoshi、Tsutsui Kazuyoshi
  • Journal Title: Frontiers in Endocrinology Volume: 10 Pages: 1-9
  • DOI: 10.3389/fendo.2019.00110
  • Peer Reviewed / Open Access
• [Presentation] Circadian regulation in brown adipose tissue (2019)
  • Author(s): You Lee Son
  • Organizer: BBRSC-JAPAN partnering workshop
  • Int'l Joint Research / Invited
• [Presentation] 脂肪細胞の褐色化における概日時計の役割 (2019)
  • Author(s): 孫ユリ、羽鳥恵
  • Organizer: 第19回日本抗加齢医学会総会
• [Book] 診療で役立つ！ 近視進行予防のサイエンス 第3章 「5．近視とサーカディアンリズム p.141-148」 (2019)
  • Author(s): 孫ユリ、羽鳥恵（編集：坪田 一男）
  • Total Pages: 192
  • Publisher: 金原出版
  • ISBN: 9784307351713