断食中の適応行動の調節は,下垂体 Foxa2 によって行われます
Jose P Silva1, Ferdinand von Meyenn, Jessica Howell
1The Rockefeller University, Laboratory of Metabolic Diseases, 1230 York Avenue, New York, New York 10021, USA.
Nature
|December 4, 2009
まとめ
フォークヘッドボックス転写因子Foxa2は,オレキシンとメラニン濃縮ホルモン (MCH) の発現を制御することによって,食事の行動を調節します. この転写因子は脳内の代謝センサーとして作用し,食物摂取と代謝に影響を与えます.
科学分野:
- 神経科学は神経科学である.
- メタボリック・レギュレーション
- 分子生物学は分子生物学である.
背景:
- 横部下垂体領域は,食事の行動,覚醒,動機づけの行動を調節する重要な脳領域です.
- オレキシンとメラニン濃縮ホルモン (MCH) は,横向性下垂体にある神経ペプチドで,食事によって抑制され,断食中に放出されます.
- 栄養関連の信号と神経ペプチドの発現を統合する正確な分子機構は不明である.
研究 の 目的:
- 横垂体下垂体におけるオレキシンおよびMCH発現の調節における転写因子Foxa2の役割を調査する.
- インスリンシグナル伝達がFoxa2の活性とその後の神経ペプチド発現にどのように影響するか解明する.
- Foxa2の操作が食事の行動,代謝,およびグルコースホメオスタシスに与える影響を決定する.
主な方法:
- 構成的および条件付き活性化モデルを含むFoxa2機能を研究するためにマウスの遺伝子操作を使用しました.
- Foxa2がMCHとオレキシン遺伝子のプロモーターに結合することを調べました.
- Foxa2の活性化が食品消費,体質,運動,インスリン感受性に及ぼす影響を評価した.
主要な成果:
- Foxa2は,オレクシンとMCHの発現を直接調節し,プロモーターと結合する.
- インスリンシグナリングは,Foxa2の核排除を促進し,MCHとオレクシン発現を栄養状態と肥満状態で減少させます.
- Foxa2の構成的または条件付きの活性化により,MCHとオレキシン発現が増加し,身体活動の増加とともに,食物摂取,代謝,インスリン感受性の向上につながった.
結論:
- Foxa2は,側下垂体領域の重要な代謝センサーとして機能します.
- Foxa2は代謝信号を統合して,食事の行動,エネルギー消費,生理学的反応を調節します.
- Foxa2のターゲティングは,肥満や糖尿病などの代謝障害の治療の可能性を提示する可能性があります.
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