The very high energy demand of the heart is primarily met by ATP production from mitochondrial oxidative phosphorylation, with glycolysis providing a smaller amount of ATP production. This ATP production is markedly altered in heart failure, primarily due to a decrease in mitochondrial oxidative metabolism. Although an increase in glycolytic ATP production partly compensates for the decrease in mitochondrial ATP production, the failing heart faces an energy deficit, that contributes to the severity of contractile dysfunction. The relative contribution of the different fuels for mitochondrial ATP production dramatically changes in the failing heart, which depends to a large extent on the type of heart failure. A common metabolic defect in all forms of heart failure (including HFrEF, HFpEF, and diabetic cardiomyopathies) is a decrease in mitochondrial oxidation of pyruvate originating from glucose (i.e. glucose oxidation). This decrease in glucose oxidation occurs regardless of whether glycolysis is increased, resulting in an uncoupling of glycolysis from glucose oxidation that can decrease cardiac efficiency. The mitochondrial oxidation of fatty acids by the heart increases or decreases, depending on the type of heart failure. For instance, in HFpEF and diabetic cardiomyopathies myocardial fatty acid oxidation increases, while in HFrEF myocardial fatty acid oxidation either decreases or remains unchanged. The oxidation of ketones (which provides the failing heart with an important energy source) also differs depending on the type of heart failure, being increased in HFrEF, and decreased in HFpEF and diabetic cardiomyopathies. The alterations in mitochondrial oxidative metabolism and glycolysis in the failing heart are due to transcriptional changes in key enzymes involved in the metabolic pathways, as well as alterations in redox state, metabolic signaling, and posttranslational epigenetic changes in energy metabolic enzymes. Of importance, targeting the mitochondrial energy metabolic pathways has emerged as a novel therapeutic approach to improving cardiac function and cardiac efficiency in the failing heart.

中文翻译：

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心肌能量代谢的进展：心力衰竭及其他领域的代谢重塑


心脏非常高的能量需求主要由线粒体氧化磷酸化产生的 ATP 来满足，而糖酵解提供的 ATP 产生量较少。这种 ATP 产生在心力衰竭中发生显著改变，主要是由于线粒体氧化代谢减少。尽管糖酵解 ATP 产生的增加部分补偿了线粒体 ATP 产生的减少，但衰竭的心脏面临能量不足，这会导致收缩功能障碍的严重程度。不同燃料对线粒体 ATP 产生的相对贡献在衰竭的心脏中发生了巨大变化，这在很大程度上取决于心力衰竭的类型。所有形式的心力衰竭（包括 HFrEF、HFpEF 和糖尿病心肌病）的常见代谢缺陷是源自葡萄糖的丙酮酸线粒体氧化减少（即葡萄糖氧化）。无论糖酵解是否增加，葡萄糖氧化都会发生这种减少，导致糖酵解与葡萄糖氧化解耦，从而降低心脏效率。心脏对脂肪酸的线粒体氧化增加或减少，具体取决于心力衰竭的类型。例如，在 HFpEF 和糖尿病心肌病中，心肌脂肪酸氧化增加，而在 HFrEF 中，心肌脂肪酸氧化减少或保持不变。酮体的氧化（为衰竭的心脏提供重要的能量来源）也因心力衰竭的类型而异，在 HFrEF 中增加，在 HFpEF 和糖尿病心肌病中降低。 衰竭心脏中线粒体氧化代谢和糖酵解的改变是由于代谢途径中涉及的关键酶的转录变化，以及能量代谢酶的氧化还原状态、代谢信号传导和翻译后表观遗传变化的改变。重要的是，靶向线粒体能量代谢途径已成为一种改善衰竭心脏心脏功能和心脏效率的新型治疗方法。