転写協活性化剤PGC-1αは,哺乳類の時計とエネルギー代謝を統合しています
Chang Liu1, Siming Li, Tiecheng Liu
1Life Sciences Institute and Department of Cell & Developmental Biology, University of Michigan Medical Center, Ann Arbor, Michigan 48109, USA.
Nature
|May 4, 2007
まとめ
ペロキシソーム増殖器活性化受容体ガンマ共活性化剤1-α (PGC-1alpha) は,哺乳類の昼夜時計とエネルギー代謝の調節に不可欠です. 肝臓と筋肉におけるリズム的な発現は,これらの重要な生理学的プロセスを統合します.
科学分野:
- 分子生物学は分子生物学である.
- クロノバイオロジー クロノバイオロジー
- メタボリズムは
背景:
- 哺乳類の昼夜時計は,グルコース,脂質,ミトコンドリア機能を含むエネルギー代謝を制御する.
- シルカディアンリズムと代謝経路を結びつける分子機構は完全に理解されていません.
研究 の 目的:
- PGC-1alpha (Ppargc1a) がエネルギー代謝の昼夜調節における役割を調査する.
- PGC-1αとコアクロック遺伝子発現の関係を解明する.
主な方法:
- マウスの肝臓と骨格筋におけるPGC-1αのリズム表現分析.
- ROR核受容体経由で時計遺伝子発現 (Bmal1,Rev-erbalpha) にPGC-1αの影響を調査する.
- PGC-1αノックアウトマウスと肝臓特異的なノックダウンモデルのフェノタイプ分析.
- PGC-1α欠乏した線維芽細胞における細胞自律的なクロック機能の評価.
主要な成果:
- PGC-1alphaはマウスの肝臓と骨格筋でリズム表現を示す.
- PGC-1alphaは,ROR核受容体と相互作用することによって,時計遺伝子Bmal1とRev-erbalphaを同活性化します.
- PGC-1αが欠けているマウスは,活動,体温,代謝率における昼間のリズムが乱れていることを示す.
- 異常な時計遺伝子発現と代謝遺伝子失調は,PGC-1α欠乏したマウスで観察されました.
- PGC-1αは,細胞自律的な昼夜時計機能に不可欠です.
結論:
- PGC-1alphaは,哺乳類の昼間時計とエネルギー代謝を統合する重要な調節体として特定されています.
- リズム的なPGC-1α発現は,生理学的リズムと代謝的恒常性を維持するために不可欠です.
- この研究は,昼間の生物学と代謝制御の間の重要な分子関連性を明らかにしています.
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