アセチル-CoAカルボキシラーゼ2が欠けているマウスの脂肪酸の継続的な酸化と脂肪の蓄積の減少
L Abu-Elheiga1, M M Matzuk, K A Abo-Hashema
1Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Science (New York, N.Y.)
|April 3, 2001
まとめ
アセチル-コアカルボキシラーゼ2 (ACC2) が欠けていたマウスは,脂肪酸の酸化が増加し,体脂肪が減少した. これは,ACC2をターゲットにすることが,体重管理のための戦略である可能性があることを示唆しています.
科学分野:
- バイオケミストリー バイオケミストリー
- メタボリズムは
- 生理学 生理学とは
背景:
- マロニル共酵素A (malonyl-CoA) は,エネルギーバランスを調節する重要な代謝物質です.
- アセチル-CoAカルボキシラーゼ (ACC1およびACC2) はマロニル-CoAを産生する.
研究 の 目的:
- エネルギーホメオスタシスにおけるACC2の生理学的役割を調査する.
- 脂肪酸の代謝と脂肪の蓄積に対するACC2欠乏の影響を決定する.
主な方法:
- Acc2-/-変異マウスの生成と分析.
- 心臓と筋肉におけるマロニル-CoA濃度の測定.
- 孤立した筋肉における脂肪酸酸化率の評価.
- 脂肪組織の脂肪含有量の定量化.
主要な成果:
- Acc2-/-マウスは正常な寿命,脂肪酸酸化の強化,脂肪質の減少を示した.
- マロニル-コア濃度は,Acc2-/-マウスの心臓と筋肉で有意に低かった.
- インスリンが脂肪酸の酸化に影響を及ぼさなかったのは,Acc2-/-筋肉の脂肪酸酸化が減少した野生型の筋肉とは異なり,Acc2-/-筋肉の脂肪酸酸化は影響しなかった.
- アク2欠乏マウスは,野生型の対照群と比較して,50%の脂肪を蓄積した.
結論:
- ACC2は,マロニル-CoAレベルと脂肪酸代謝の調節に重要な役割を果たしています.
- ACC2の欠乏は脂肪酸の酸化を増加させ,脂肪の蓄積を減少させます.
- ACC2の薬理学的阻害は,体脂肪を減らすための治療戦略を表す可能性があります.
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