Cardiovascular Research Centre, Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.
Cardiovascular Research Centre, Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada; Department of Pharmacology, College of Medicine, University of Diyala, Diyala, Iraq.
Biochim Biophys Acta Mol Cell Biol Lipids. 2020 Dec;1865(12):158813. doi: 10.1016/j.bbalip.2020.158813. Epub 2020 Sep 10.
The high energy demands of the heart are met primarily by the mitochondrial oxidation of fatty acids and glucose. However, in heart failure there is a decrease in cardiac mitochondrial oxidative metabolism and glucose oxidation that can lead to an energy starved heart. Ketone bodies are readily oxidized by the heart, and can provide an additional source of energy for the failing heart. Ketone oxidation is increased in the failing heart, which may be an adaptive response to lessen the severity of heart failure. While ketone have been widely touted as a "thrifty fuel", increasing ketone oxidation in the heart does not increase cardiac efficiency (cardiac work/oxygen consumed), but rather does provide an additional fuel source for the failing heart. Increasing ketone supply to the heart and increasing mitochondrial ketone oxidation increases mitochondrial tricarboxylic acid cycle activity. In support of this, increasing circulating ketone by iv infusion of ketone bodies acutely improves heart function in heart failure patients. Chronically, treatment with sodium glucose co-transporter 2 inhibitors, which decreases the severity of heart failure, also increases ketone body supply to the heart. While ketogenic diets increase circulating ketone levels, minimal benefit on cardiac function in heart failure has been observed, possibly due to the fact that these dietary regimens also markedly increase circulating fatty acids. Recent studies, however, have suggested that administration of ketone ester cocktails may improve cardiac function in heart failure. Combined, emerging data suggests that increasing cardiac ketone oxidation may be a therapeutic strategy to treat heart failure.
心脏的高能量需求主要通过脂肪酸和葡萄糖的线粒体氧化来满足。然而，在心力衰竭中，心脏线粒体氧化代谢和葡萄糖氧化减少，可能导致心肌能量饥饿。酮体容易被心脏氧化，可为衰竭的心脏提供额外的能量来源。心力衰竭时酮体氧化增加，这可能是一种适应性反应，可减轻心力衰竭的严重程度。虽然酮体已被广泛宣传为“节俭的燃料”，但增加心脏中的酮体氧化并不会增加心脏效率（心脏做功/耗氧量），而是为衰竭的心脏提供了额外的燃料来源。增加心脏的酮供应和增加线粒体酮氧化可增加线粒体三羧酸循环活性。支持这一观点的是，通过静脉输注酮体急性增加循环酮可改善心力衰竭患者的心脏功能。从长远来看，用钠-葡萄糖共转运蛋白 2 抑制剂治疗，可降低心力衰竭的严重程度，也会增加酮体向心脏的供应。尽管生酮饮食会增加循环酮水平，但在心力衰竭中观察到对心脏功能的最小益处，这可能是由于这些饮食方案还会显著增加循环脂肪酸。然而，最近的研究表明，酮酯鸡尾酒的给药可能会改善心力衰竭患者的心脏功能。综上所述，新出现的数据表明，增加心脏酮体氧化可能是治疗心力衰竭的一种治疗策略。
