FoxO转录因子在骨骼肌稳态中的作用及运动训练调控

Functions of FoxO Transcription Factors in Skeletal Muscle Homeostasis and Exercise-Related Regulation

进化上高度保守的FoxO转录因子家族对维持细胞稳态起到重要的作用,该家族包括FoxO1、FoxO3、FoxO4和FOXO6。综述了FoxO转录因子在骨骼肌稳态中的关键作用。FoxO1和FoxO3通过控制糖脂分解及线粒体代谢,起到肌肉能量代谢的核心调控因子的作用。它们同时也调控蛋白质合成、降解,影响肌纤维类型、肌肉量。根据它们的激活水平,FoxO蛋白展示出不同的功能。FoxO蛋白也是机体运动适应所必需的,不同的运动训练方式对其产生不同的影响。FoxO过度激活可能会导致许多疾病,如代谢紊乱、肌肉萎缩等。更好地理解FoxO转录因子的功能,将会对促进防控许多病理条件下(如肌肉制动、去神经支配状态、神经肌肉疾病、衰老、糖尿病、艾滋病、癌症等)肌肉耗费治疗手段的发展起到重要作用。

FoxOs are highly conserved transcription factors with significant roles in cellular homeostasis. The four FoxO members are FoxO1, FoxO3, FoxO4, and FOXO6. This review discusses the central role of these proteins in the control of skeletal muscle homeostasis. FoxO1 and FoxO3 are key factors of muscle energy homeostasis through the control of glyco- lyric and lipolytic flux, and mitochondrial metabolism. They are important regulators of muscle fiber types and protein breakdown. According to their activation level,FoxO proteins can exhibit different functions. For example, a basal level of FoxO factors is essential for cellular homeostasis and these proteins are required for muscle adaptation to exercise. Different types of exercise have diverse effects on them. However, exacerbated activation may be present in many diseases, resulting in atrophy and metabolic disorders. A better understanding of these transcription factors functions will facilitate the develop- ment of new therapeutic approaches to prevent or limit the muscle wasting that prevails in multiple pathological states, such as immobilization, denervated conditions, neuromuscular disease, aging, diabetes, AIDS, and cancer.