ミトフシンによって制御されるミトコンドリアのダイナミクスは,Agrpの神経活動と食事による肥満を調節する
Marcelo O Dietrich1, Zhong-Wu Liu, Tamas L Horvath
1Program in Integrative Cell Signaling and Neurobiology of Metabolism, Section of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90035, Brazil.
Cell
|October 1, 2013
まとめ
アグウティ関連タンパク質 (Agrp) のニューロンにおけるミトコンドリア動態は,エネルギーバランスを調節する. Agrpニューロンのミトコンドリア融合を妨害することは,ニューロンの活動に影響を与え,高脂肪食で体重増加を減少させます.
科学分野:
- 細胞生物学 細胞生物学
- 神経科学は神経科学である.
- メタボリズムは
背景:
- ミトコンドリアは,細胞のエネルギー代謝と完全性にとって極めて重要です.
- アグーティ関連タンパク質 (Agrp) ニューロンは,食欲を調節する重要な酸素細胞です.
- ミトコンドリアのダイナミクス,すなわち融合と分裂は,細胞機能に不可欠である.
研究 の 目的:
- 異なる栄養状態におけるAgrpニューロンにおけるミトコンドリアダイナミクスの役割を調査する.
- Agrpニューロンにおけるミトコンドリア融合タンパク質 (Mfn1,Mfn2) に干渉する影響を決定する.
- 全体の体エネルギー代謝に対するAgrpニューロンミトコンドリアダイナミクスの貢献を解明する.
主な方法:
- 栄養状態におけるAgrpおよびプロオピオメラノコルチン (POMC) ニューロンにおけるミトコンドリア数とサイズの分析.
- Agrpニューロンにおけるミトフーシン1 (Mfn1) またはミトフーシン2 (Mfn2) の細胞特異的なノックダウン.
- Agrpニューロン活動の電気生理学的記録とATPレベルの評価.
- 高脂肪食 (HFD) を摂取したノックアウトマウスの体重増加と脂肪質の評価.
主要な成果:
- ミトコンドリア数は減少し,Agrpニューロンのサイズは増加し,断食状態から過度の栄養状態に変化し,POMCニューロンでは逆の変化がありました.
- AgrpニューロンにおけるMfn1またはMfn2のノックダウンにより,HFD中にミトコンドリアの形態が変化し,ニューロンの電気活動が低下する.
- ATP投与は,Agrpニューロンの電気活動の障害を逆転させました.
- Agrp特異的なMfn1またはMfn2ノックアウトを持つマウスは,HFDで体重増加が減少し,脂肪質が減少した.
結論:
- Mfn1とMfn2によって調節されるミトコンドリアのダイナミクスは,Agrpニューロン機能において重要な役割を果たします.
- Agrpニューロンのこれらのミトコンドリアの変化は,細胞タイプに特異的で,栄養状態に反応します.
- AgrpニューロンのMfn1とMfn2は,全身のエネルギー代謝と体重制御の中央調節に不可欠です.
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