乳酸代谢在骨骼肌能量稳态及运动调控中的作用研究
能量代谢稳态是维持机体正常生理功能的基础。随着全球人口的增长和老龄化的加剧,衰老引起的代谢紊乱已成为重要的公共健康挑战。通过运动干预,可以有效缓解衰老过程中的肌肉退化。运动过程中骨骼肌细胞通过糖酵解释放到循环中的乳酸不仅可以作为能源物质,也有可能是一种信号分子参与不同细胞的基因表达的调节和蛋白水平的调控。本研究基于人体三角肌骨骼肌组织的多样本基因表达测序结果,发现在年老人群的骨骼肌中的糖代谢途径发生变化,其中乳酸脱氢酶LDHA/LDHB的含量发生显著变化,提示乳酸可能在骨骼肌衰老过程中发挥重要作用。随后我们通过对骨骼肌条件敲除Ldhb(LdhbMKO)进行运动能力检测,验证乳酸对骨骼肌功能的影响。结果提示在运动过程中骨骼肌中的糖代谢途径被激活时,如果乳酸不能被有效代谢(LdhbMKO),将导小鼠的致氧耗增多;同时ATGL蛋白和乳酸化蛋白上调,进而激活脂代谢途径,为骨骼肌提供更多的能量来源。实验结果对于从乳酸代谢角度研究骨骼肌的功能维持和寻找运动能力的提升的办法具有潜在的提示作用。
Energy metabolism homeostasis is fundamental to maintaining normal physiological functions. With the growth of the global population and the intensification of aging, metabolic disorders caused by aging have become a significant public health challenge. Exercise intervention has been shown to effectively mitigate muscle degeneration during aging. During exercise, lactate released into circulation through glycolysis in skeletal muscle cells not only serves as an energy substrate but may also function as a signaling molecule involved in regulating gene expression and protein levels in various cell types. In this study, based on multi-saThe Role of Lactate Metabolism in Skeletal Muscle Energy Homeostasis and Exercise Regulationmple gene expression sequencing of the deltoid skeletal muscle tissue in humans, we found that the glycolytic pathway in skeletal muscle undergoes changes in the elderly population. Notably, the levels of lactate dehydrogenase isoforms LDHA and LDHB exhibited significant alterations, suggesting that lactate may play a crucial role in skeletal muscle aging. To further investigate this, we conducted exercise performance assessments in skeletal muscle-specific Ldhb knockout (LdhbMKO) mice to examine the impact of lactate on skeletal muscle function. Our results indicate that when the glycolytic pathway in skeletal muscle is activated during exercise, impaired lactate metabolism (LdhbMKO) leads to increased oxygen consumption in mice. Additionally, ATGL protein and lactylated proteins were upregulated, thereby activating lipid metabolism pathways to provide an alternative energy source for skeletal muscle. These findings provide potential insights into the role of lactate metabolism in maintaining skeletal muscle function and offer implications for strategies aimed at enhancing exercise performance.
罗岭、贾志浩
苏州大学医学院(剑桥-苏大基因资源组中心),江苏省苏州市,215123苏州大学医学院(剑桥-苏大基因资源组中心),江苏省苏州市,215123
基础医学生物化学生理学
运动骨骼肌糖脂代谢LDHB乳酸代谢
exerciseskeletal muscleglucose and lipid metabolismLDHBlactate metabolism
罗岭,贾志浩.乳酸代谢在骨骼肌能量稳态及运动调控中的作用研究[EB/OL].(2025-04-15)[2025-04-30].http://www.paper.edu.cn/releasepaper/content/202504-110.点此复制
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