Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
Biochim Biophys Acta Mol Basis Dis. 2020 Jun 1;1866(6):165739. doi: 10.1016/j.bbadis.2020.165739. Epub 2020 Feb 19.
The ketone bodies, d-β-hydroxybutyrate and acetoacetate, are soluble 4-carbon compounds derived principally from fatty acids, that can be metabolised by many oxidative tissues, including heart, in carbohydrate-depleted conditions as glucose-sparing energy substrates. They also have important signalling functions, acting through G-protein coupled receptors and histone deacetylases to regulate metabolism and gene expression including that associated with anti-oxidant activity. Their concentration, and hence availability, increases in diabetes mellitus and heart failure. Whilst known to be substrates for ATP production, especially in starvation, their role(s) in the heart, and in heart disease, is uncertain. Recent evidence, reviewed here, indicates that increased ketone body metabolism is a feature of heart failure, and is accompanied by other changes in substrate selection. Whether the change in myocardial ketone body metabolism is adaptive or maladaptive is unknown, but it offers the possibility of using exogenous ketones to treat the failing heart.
酮体，即 D-β-羟丁酸和乙酰乙酸，是主要来源于脂肪酸的可溶性 4 碳化合物，在碳水化合物耗竭的情况下，可以作为葡萄糖节约能量底物被许多氧化组织（包括心脏）代谢。它们还具有重要的信号功能，通过 G 蛋白偶联受体和组蛋白去乙酰化酶来调节代谢和基因表达，包括与抗氧化活性相关的基因表达。它们的浓度，因此其可用性，在糖尿病和心力衰竭中增加。虽然已知是 ATP 产生的底物，特别是在饥饿时，但它们在心脏中的作用及其在心脏病中的作用尚不确定。这里综述的最新证据表明，增加酮体代谢是心力衰竭的一个特征，同时伴随着底物选择的其他变化。心肌酮体代谢的变化是适应性的还是适应性不良的尚不清楚，但它为使用外源性酮体治疗衰竭的心脏提供了可能性。
