短鎖脂肪酸 は 衰え て いる 心臓 の ケトン 酸化 を 追い越す
Andrew N Carley1, Santosh K Maurya1, Matthew Fasano1
1Davis Heart and Lung Research Institute and Department of Internal Medicine, The Ohio State University College of Medicine, Columbus (A.N.C., S.K.M., M.F., Y.W., E.D.L.).
Circulation
|February 19, 2021
まとめ
短鎖脂肪酸 (SCFA) は 衰弱した心臓のケトンより容易に酸化され,新しいエネルギー源を提供します. この研究は,エネルギー不足の心臓の代替燃料として SCFA を検討しています.
科学分野:
- 心臓病科
- 生物化学
- 代謝に関する研究
背景:
- 衰弱した心臓は,カーニチンパルミトイルトランスフェラーゼ1 (CPT1) の活性が低下したため,長鎖脂肪酸 (LCFA) の酸化が低下しています.
- ATP生成のための代替炭素源として,ケトン酸化が心不全で上昇します.
- 短鎖脂肪酸 (SCFA) は,CPT1を回避することで,エネルギー生産を支援することもできます.
研究 の 目的:
- 心臓不全の治療における代替エネルギー源としてのSCFAの可能性を調査する.
- 健康な心臓と肥大した心臓の両方で,SCFAとケトンの酸化率を比較する.
- SCFAとケトン代謝に関連する酵素発現の適応的変化を調べる.
主な方法:
- ラットでは,横動脈収縮 (TAC) による心筋縮と機能不全が誘発された.
- 隔離された心臓は,グルコースとパルミテート (LCFA) とともに,13Cラベルブチラート (SCFA) またはD3-ヒドロキシブチラート (ケトン) を注入した.
- 13C核磁共鳴光譜を用いて酸化率を測定し,酵素発現を分析した.
主要な成果:
- TACはアセチル-CoAの生産にケトンの寄与を増加させ,病理的過剰化を誘発した.
- ブチラート (SCFA) の酸化はケトンの酸化より15%高く,偽心臓では15%高かった.
- SCFAとケトンの酸化はLCFAの酸化を犠牲にして増加し,SCFAを注入した衰弱した心臓ではLCFAのアセチル-CoAへの貢献が減少した.
結論:
- 短鎖脂肪酸 (SCFA) は,衰弱した心臓でケトンよりも容易に酸化されます.
- SCFAは 衰弱した心臓のエネルギー生産に 有望な,まだ未開発の 代替炭素源です
- 衰弱した心臓の代謝適応は,SCFAやケトンなどのCPT1をバイパスする基質の酸化を好みます.
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