Takada Shingo, Sabe Hisataka, Kinugawa Shintaro
Faculty of Lifelong Sport, Department of Sports Education, Hokusho University, Ebetsu, Japan.
Department of Molecular Biology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Front Cardiovasc Med. 2020 May 12;7:79. doi: 10.3389/fcvm.2020.00079. eCollection 2020.
Chronic diseases, including heart failure (HF), are often accompanied with skeletal muscle abnormalities in both quality and quantity, which are the major cause of impairment of the activities of daily living and quality of life. We have shown that skeletal muscle abnormalities are a hallmark of HF, in which metabolic pathways involving phosphocreatine and fatty acids are largely affected. Not only in HF, but the dysfunction of fatty acid metabolism may also occur in many chronic diseases, such as arteriosclerosis, as well as through insufficient physical exercise. Decreased fatty acid catabolism affects adenosine triphosphate (ATP) production in mitochondria, via decreased activity of the tricarboxylic acid cycle; and may cause abnormal accumulation of adipose tissue accompanied with hyperoxidation and ectopic lipid deposition. Such impairments of lipid metabolism are in turn detrimental to skeletal muscle, which is hence a chicken-and-egg problem between skeletal muscle and HF. In this review, we first discuss skeletal muscle abnormalities in HF, including sarcopenia; particularly their association with lipid metabolism and adipose tissue. On the other hand, the precise mechanisms involved in metabolic reprogramming and dysfunction are beginning to be understood, and an imbalance of daily nutritional intake of individuals has been found to be a causative factor for the development and worsening of HF. Physical exercise has long been known to be beneficial for the prevention and even treatment of HF. Again, the molecular mechanisms by which exercise promotes skeletal muscle as well as cardiac muscle functions are being clarified by recent studies. We propose that it is now the time to develop more "natural" methods to prevent and treat HF, rather than merely relying on drugs and medical interventions. Further analysis of the basic design of and molecular mechanisms involved in the human body, particularly the inextricable association between physical exercise and the integrity and functional plasticity of skeletal and cardiac muscles is required.
包括心力衰竭（HF）在内的慢性疾病，常常伴随着骨骼肌在质量和数量上的异常，而这正是日常生活活动受损和生活质量下降的主要原因。我们已经表明，骨骼肌异常是HF的一个标志，其中涉及磷酸肌酸和脂肪酸的代谢途径受到很大影响。不仅在HF中如此，脂肪酸代谢功能障碍也可能发生在许多慢性疾病中，如动脉硬化，以及因体育锻炼不足导致的情况。脂肪酸分解代谢的降低会通过三羧酸循环活性的降低影响线粒体中三磷酸腺苷（ATP）的产生；并可能导致脂肪组织异常堆积，伴有过氧化和异位脂质沉积。这种脂质代谢的损害反过来又对骨骼肌有害，因此骨骼肌和HF之间存在着一个先有鸡还是先有蛋的问题。在这篇综述中，我们首先讨论HF中的骨骼肌异常，包括肌肉减少症；特别是它们与脂质代谢和脂肪组织的关联。另一方面，参与代谢重编程和功能障碍的确切机制正开始被理解，并且已经发现个体日常营养摄入的不平衡是HF发生和恶化的一个致病因素。长期以来，体育锻炼一直被认为对HF的预防甚至治疗有益。同样，近期研究正在阐明运动促进骨骼肌以及心肌功能的分子机制。我们认为，现在是时候开发更多“自然”的方法来预防和治疗HF了，而不仅仅依赖于药物和医学干预。需要进一步分析人体的基本设计和所涉及的分子机制，特别是体育锻炼与骨骼肌和心肌的完整性及功能可塑性之间的紧密联系。
