PRDM16-C/EBP-β転写複合体によるミオブラストの茶色脂肪への切り替えを開始する
Shingo Kajimura1, Patrick Seale, Kazuishi Kubota
1Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115, USA.
Nature
|July 31, 2009
まとめ
PRDM16とC/EBP-βは,細胞運命を切り替える複合体を形成し,前駆体から茶色の脂肪細胞を生成します. この発見は,肥満と2型糖尿病に対する潜在的な新しい治療法を提供します.
科学分野:
- 細胞生物学 細胞生物学
- メタボリズムは
- 分子生物学は分子生物学である.
背景:
- 茶色の脂肪細胞は,熱としてエネルギーを放散し,風邪と肥満と闘います.
- PRDM16タンパク質は,茶色の脂肪の決定と微分を誘導することが知られている.
- 茶色脂肪の発達スイッチを制御する正確な分子機構は不明のままである.
研究 の 目的:
- PRDM16が細胞運命をブラウン脂肪に切り替えることを制御する分子メカニズムを解明する.
- 茶色脂肪の発達のための転写複合体の形成におけるPRDM16の役割を調査する.
- PRDM16とC/EBP-βが非脂肪細胞における茶色脂肪の形成を誘発する可能性を評価する.
主な方法:
- PRDM16とC/EBP-βの相互作用を調査しました.
- 繊維芽細胞におけるPRDM16とC/EBP-βの強制発現を利用した.
- 遺伝子組み換え繊維芽細胞をマウスに移植し,子宮外脂肪パッドを形成しました.
- フッ素酸化グルコース (FDG) によるポジトロン放出トモグラフィー (PET) を用いて,合成茶色脂肪組織におけるグルコース摂取量を評価した.
主要な成果:
- PRDM16は,C/EBP-β (LAP) の活性型とトランスクリプション複合体を形成する.
- このPRDM16-C/EBP-β複合体は,細胞運命をミオブラスティック前駆体からブラウン脂肪細胞に切り替える上で極めて重要です.
- PRDM16とC/EBP-βの強制発現は,マウスとヒトの線維芽細胞で機能的な茶色の脂肪プログラムを引き起こした.
- 移植された線維芽細胞は子宮の外部茶色脂肪組織を形成し,内生的な茶色脂肪と同じようなグルコース吸収を示した.
結論:
- PRDM16-C/EBP-β複合体は,ミオブラスティック前駆体から茶色の脂肪の形成を開始します.
- このメカニズムは,茶色の脂肪の生成のための新しい経路を提供します.
- 発見は,この複合体を操作することによって,肥満と2型糖尿病の潜在的な治療戦略を示唆しています.
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