The potential role of melanopsin in metabolic regulation

2020 Fiscal Year Final Research Report

• 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
• Keywords: メラノプシン (Opn4) / 概日時計 / 代謝 / 脂肪

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.

Free Research Field

分子内分泌

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。