サクシネートの蓄積は脂肪組織熱生成の活性化を制御する
Evanna L Mills1,2, Kerry A Pierce3, Mark P Jedrychowski1,2
1Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
Nature
|July 20, 2018
まとめ
脂肪組織にサクシネートの蓄積は,従来の経路とは独立して発熱を引き起こします. この発見により 肥満と闘い 代謝の健康を改善する 新しい方法が明らかになりました
科学分野:
- 代謝経路
- 脂肪組織生物学
- 熱生成
背景:
- 茶色とベージュの脂肪組織は 代謝疾患と闘います
- 循環型AMPタンパク質キナーゼAによるアドレナージ信号は熱生成を誘発する.
- この経路は臨床研究の焦点となっています
研究 の 目的:
- 脂肪組織の発熱を制御する新しい代謝経路を特定する.
- サーモゲネシスにおけるサクシネートの役割を調査する.
- 代謝障害の治療対象としてサクシネートを研究する.
主な方法:
- 比較メタボロミクスアプローチ
- マウスの体内試験
- 反応性酸素種生成とUCP1依存の熱生成の分析
主要な成果:
- サクシネート蓄積は脂肪組織発熱のサインです.
- サクシネートは アドレナージ信号から独立して 発熱呼吸を活性化します
- 体系的なサクシネート投与は熱生成を開始し,肥満から保護します.
- サクシネート脱水素酵素によるサクシネート酸化は熱生成に不可欠である.
結論:
- サクシネートは脂肪組織発熱の独立した代謝調節剤です.
- サクシネートは全身生成の熱生成分子として作用する.
- 肥満と代謝機能障害の治療には,サクシネートの薬理学的上昇が潜在的戦略である.
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