クレアチン駆動の基板サイクルは,ベージュ脂肪のエネルギー消費と発熱を促進します
Lawrence Kazak1, Edward T Chouchani1, Mark P Jedrychowski2
1Dana-Farber Cancer Institute, Boston, MA 02115, USA; Department of Cell Biology, Harvard University Medical School, Boston, MA 02115, USA.
Cell
|October 27, 2015
まとめ
クレアチンの代謝を明らかにした.
科学分野:
- 脂肪組織生物学
- ミトコンドリア機能
- 代謝の調節
背景:
- 熱性茶色とベージュの脂肪組織は 熱としてエネルギーを放散し 肥満と糖尿病との闘いに不可欠です
- これらの組織における 寒さによる適応を理解することは 代謝研究の鍵です
研究 の 目的:
- 定量プロテオミクスを用いて,寒さに曝露したときに,茶色とベージュの脂肪組織における機能的適応を調査する.
- 熱生成とエネルギー消費に関わる新しい代謝経路を特定する.
主な方法:
- 脂肪組織におけるタンパク質発現を分析するための定量ミトコンドリアプロテオミクス.
- ミトコンドリアの呼吸と酵素の活性を測定する
- クレアチンの代謝の役割を評価するための遺伝的および薬物学的操作.
主要な成果:
- アルギニンとクレアチンの代謝は ベージュ色の脂肪組織で 特徴的に確認されました
- クレアチンはベージュ色の脂肪ミトコンドリアの呼吸を促進し,特にADPが制限されている場合です.
- ミトコンドリアのクレアチンキナーゼと クレアチンの代謝遺伝子をマウスのベージュ色脂肪で高調化する.
- クレアチンのレベルが低下すると,エネルギー消費と脂肪組織の代謝率が低下します.
- クレアチンの代謝遺伝子はUCP1依存の発熱が妨げられ,クリエチンの減少はUcp1欠乏したマウスの体温を下げます.
結論:
- クレアチンの代謝の無駄なサイクルは脂肪組織のエネルギー消費と関連しています.
- クレアチンの代謝は,熱的ホメオスタシスと適応的発熱に重要な役割を果たします.
- クレアチンの代謝をターゲットにすることで,代謝障害の治療策を提供することができる.
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