Qi Zhen, Liu Xi, Chen Yifen, Zhang Linglin, Yang Longhe, Huang Caihua, Lin Donghai
Key Laboratory of Chemical Biology of Fujian Province, Department of Chemical Biology, College of Chemistry and Chemical Engineering,Xiamen University, Xiamen, China.
Technical Innovation Center for Utilization of Marine Biological Resources, Third Institute of Oceanography, Ministry of Natural Resources, Xiamen, China.
Mol Cell Biol. 2025 Sep 17:1-19. doi: 10.1080/10985549.2025.2551616.
Lactate, historically considered a metabolic byproduct, has emerged as a key regulator of muscle physiology and metabolism. This study explores its potential as an exercise mimetic to counteract disuse muscle atrophy (DMA) in aging skeletal muscle using a hindlimb suspension model in senescence-accelerated prone 8 (SAMP8) mice. The mice were divided into four groups: Control, lactate-treated control, hindlimb suspension, and hindlimb suspension with lactate intervention. Lactate administration preserved gastrocnemius muscle mass, restored muscle strength, and attenuated oxidative fiber atrophy. Electrophoretic and histological analyses showed increased MyHC I expression, indicating protection of oxidative fibers. Functional assessments revealed improved muscle endurance and contractile force, while metabolomic profiling identified changes in energy metabolism, amino acid metabolism, and protein synthesis pathways. Specifically, lactate improved impaired branched-chain amino acid metabolism, suggesting enhanced protein synthesis. In addition, lactate boosted Cori cycle activity, upregulated hepatic lactate transporters, and increased lactate dehydrogenase B activity, facilitating efficient lactate metabolism and gluconeogenesis. These results provide new insights into the role of lactate as a metabolic regulator and highlight its potential as a therapeutic intervention to combat exercise-induced muscle wasting and preserve muscle function in aging and immobilized individuals.
乳酸，历史上被认为是一种代谢副产物，现已成为肌肉生理和代谢的关键调节因子。本研究利用衰老加速易感性8（SAMP8）小鼠的后肢悬吊模型，探讨其作为运动模拟物以对抗衰老骨骼肌废用性肌肉萎缩（DMA）的潜力。将小鼠分为四组：对照组、乳酸处理对照组、后肢悬吊组和乳酸干预后肢悬吊组。给予乳酸可保留腓肠肌质量、恢复肌肉力量并减轻氧化纤维萎缩。电泳和组织学分析显示肌球蛋白重链I（MyHC I）表达增加，表明氧化纤维得到保护。功能评估显示肌肉耐力和收缩力有所改善，而代谢组学分析确定了能量代谢、氨基酸代谢和蛋白质合成途径的变化。具体而言，乳酸改善了受损的支链氨基酸代谢，表明蛋白质合成增强。此外，乳酸增强了科里循环活性，上调了肝脏乳酸转运体，并增加了乳酸脱氢酶B活性，促进了乳酸的有效代谢和糖异生。这些结果为乳酸作为代谢调节因子的作用提供了新的见解，并突出了其作为治疗干预措施的潜力，以对抗运动诱导的肌肉萎缩，并在衰老和固定不动的个体中维持肌肉功能。
