As a muscular pump that contracts incessantly throughout life, the heart must constantly generate cellular energy to support contractile function and fuel ionic pumps to maintain electrical homeostasis. Thus, mitochondrial metabolism of multiple metabolic substrates such as fatty acids, glucose, ketones, and lactate is essential to ensuring an uninterrupted supply of ATP. Multiple metabolic pathways converge to maintain myocardial energy homeostasis. The regulation of these cardiac metabolic pathways has been intensely studied for many decades. Rapid adaptation of these pathways is essential for mediating the myocardial adaptation to stress, and dysregulation of these pathways contributes to myocardial pathophysiology as occurs in heart failure and in metabolic disorders such as diabetes. The regulation of these pathways reflects the complex interactions of cell-specific regulatory pathways, neurohumoral signals, and changes in substrate availability in the circulation. Significant advances have been made in the ability to study metabolic regulation in the heart, and animal models have played a central role in contributing to this knowledge. This review will summarize metabolic pathways in the heart and describe their contribution to maintaining myocardial contractile function in health and disease. The review will summarize lessons learned from animal models with altered systemic metabolism and those in which specific metabolic regulatory pathways have been genetically altered within the heart. The relationship between intrinsic and extrinsic regulators of cardiac metabolism and the pathophysiology of heart failure and how these have been informed by animal models will be discussed.

中文翻译：

---

心脏代谢失调的动物模型

作为终生不断收缩的肌肉泵，心脏必须不断产生细胞能量以支持收缩功能，并为离子泵提供燃料以维持电稳态。因此，多种代谢底物（如脂肪酸、葡萄糖、酮和乳酸）的线粒体代谢对于确保 ATP 的不间断供应至关重要。多种代谢途径汇聚以维持心肌能量稳态。几十年来，人们对这些心脏代谢途径的调控进行了深入研究。这些通路的快速适应对于调节心肌对压力的适应至关重要，并且这些通路的失调会导致心肌病理生理学发生在心力衰竭和代谢紊乱（如糖尿病）中。这些通路的调节反映了细胞特异性调节通路、神经体液信号和循环中底物可用性变化之间的复杂相互作用。研究心脏代谢调节的能力取得了重大进展，动物模型在促进这一知识方面发挥了核心作用。这篇综述将总结心脏中的代谢途径，并描述它们对维持健康和疾病心肌收缩功能的贡献。该综述将总结从全身代谢改变的动物模型和心脏内特定代谢调节通路发生基因改变的动物模型中吸取的经验教训。