Elucidating molecular mechanisms of metabolism and circadian rhythm regulation by glucocorticoid receptor

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K17505
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: University of Tsukuba
• Principal Investigator: Murayama Yuki 筑波大学, 附属病院, 病院講師 (80869248)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: グルココルチコイドレセプター / ステロイド / 時計遺伝子 / 代謝 / 脂質 / 血糖

Outline of Final Research Achievements

By conducting comprehensive gene expression analysis in mouse livers treated with GR and Nr1d1 ligands, we aimed to discover a new molecular link between metabolic regulation and circadian rhythm, and establish new treatment methods that reduce side effects of GCs and improve metabolic diseases.
RNA-seq analysis was performed as a transcriptome analysis of GR / Nr1d1 ligand stimulation effect, and at the same time various hormones in the blood and lipids in the liver were measured, and based on these results, the Nr1d1 target gene that acts antagonistically to GR was extracted. Then, we verified the effect of overexpression and knockdown on the gene.

Free Research Field

代謝内分泌学

Academic Significance and Societal Importance of the Research Achievements

時計遺伝子とステロイドホルモンが関連を持つという側面から、ステロイド治療の副作用の軽減のために新たな分子メカニズムを探索した。特に時計遺伝子であり代謝にも関連のあるNr1d1との関連を元に、それぞれのリガンドを投与した実験を行い、それによる代謝パラメーターの変化や網羅的な遺伝子解析を行い、今後の治療につながる知見を得ることができた。