Tian Haili, Liu Sujuan, Ren Jun, Lee Jason Kai Wei, Wang Ru, Chen Peijie
School of Kinesiology, Shanghai University of Sport, Shanghai, China.
Department of Anatomy and Histology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
Front Physiol. 2020 Aug 11;11:949. doi: 10.3389/fphys.2020.00949. eCollection 2020.
Skeletal muscle is the largest metabolic organ in the human body and is able to rapidly adapt to drastic changes during exercise. Histone acetyltransferases (HATs) and histone deacetylases (HDACs), which target histone and non-histone proteins, are two major enzyme families that control the biological process of histone acetylation and deacetylation. Balance between these two enzymes serves as an essential element for gene expression and metabolic and physiological function. Genetic KO/TG murine models reveal that HDACs possess pivotal roles in maintaining skeletal muscles' metabolic homeostasis, regulating skeletal muscles motor adaptation and exercise capacity. HDACs may be involved in mitochondrial remodeling, insulin sensitivity regulation, turn on/off of metabolic fuel switching and orchestrating physiological homeostasis of skeletal muscles from the process of myogenesis. Moreover, many myogenic factors and metabolic factors are modulated by HDACs. HDACs are considered as therapeutic targets in clinical research for treatment of cancer, inflammation, and neurological and metabolic-related diseases. This review will focus on physiological function of HDACs in skeletal muscles and provide new ideas for the treatment of metabolic diseases.
骨骼肌是人体最大的代谢器官，能够在运动过程中迅速适应剧烈变化。组蛋白乙酰转移酶（HATs）和组蛋白去乙酰化酶（HDACs）以组蛋白和非组蛋白为作用靶点，是控制组蛋白乙酰化和去乙酰化生物学过程的两个主要酶家族。这两种酶之间的平衡是基因表达以及代谢和生理功能的关键要素。基因敲除/转基因小鼠模型显示，HDACs在维持骨骼肌代谢稳态、调节骨骼肌运动适应性和运动能力方面发挥着关键作用。HDACs可能参与线粒体重塑、胰岛素敏感性调节、代谢燃料转换的开启/关闭以及从肌生成过程协调骨骼肌的生理稳态。此外，许多肌源性因子和代谢因子受HDACs调节。在癌症、炎症以及神经和代谢相关疾病的临床治疗研究中，HDACs被视为治疗靶点。本综述将聚焦HDACs在骨骼肌中的生理功能，并为代谢性疾病的治疗提供新思路。
