The failing heart utilizes 3-hydroxybutyrate as a metabolic stress defense
The failing heart utilizes 3-hydroxybutyrate as a metabolic stress defense
复制标题
DOI：
10.1172/jci.insight.124079
复制
发表时间：
2019-02-21
期刊：
影响因子：
8
通讯作者：
Kelly, Daniel P.
中科院分区：
文献类型：
--
作者：
Horton, Julie L.;Davidson, Michael T.;Kelly, Daniel P.
有证据表明，心脏衰竭会增加酮体的利用率。我们试图确定这种燃料转变是否具有适应性。与 WT 对照组相比，无法氧化心脏中酮体 3-羟基丁酸 (3OHB) 的小鼠因禁食或压力超负荷/缺血性损伤而表现出更严重的心力衰竭。增加 3OHB 的递送可改善小鼠和进行性心力衰竭的犬起搏模型中的病理性心脏重塑和功能障碍。在限制脂肪酸水平的情况下，3OHB 被证明可以增强分离线粒体的生物能热力学。这些结果表明心脏利用 3OHB 作为代谢应激防御，并表明旨在增加向心脏输送酮的策略可能在心力衰竭的治疗中有用。
Evidence has emerged that the failing heart increases utilization of ketone bodies. We sought to determine whether this fuel shift is adaptive. Mice rendered incapable of oxidizing the ketone body 3-hydroxybutyrate (3OHB) in the heart exhibited worsened heart failure in response to fasting or a pressure overload/ischemic insult compared with WT controls. Increased delivery of 3OHB ameliorated pathologic cardiac remodeling and dysfunction in mice and in a canine pacing model of progressive heart failure. 3OHB was shown to enhance bioenergetic thermodynamics of isolated mitochondria in the context of limiting levels of fatty acids. These results indicate that the heart utilizes 3OHB as a metabolic stress defense and suggest that strategies aimed at increasing ketone delivery to the heart could prove useful in the treatment of heart failure.