PDF(Pubmed)
Abstract：
Disuse muscle atrophy (DMA) is a significant healthcare challenge characterized by progressive loss of muscle mass and function resulting from prolonged inactivity. The development of effective strategies for muscle recovery is essential. In this study, we established a DMA mouse model through hindlimb suspension to evaluate the therapeutic potential of lactate in alleviating the detrimental effects on the gastrocnemius muscle. Using NMR-based metabolomic analysis, we investigated the metabolic changes in DMA-injured gastrocnemius muscles compared to controls and evaluated the beneficial effects of lactate treatment. Our results show that lactate significantly reduced muscle mass loss and improved muscle function by downregulating Murf1 expression, decreasing protein ubiquitination and hydrolysis, and increasing myosin heavy chain levels. Crucially, lactate corrected perturbations in four key metabolic pathways in the DMA gastrocnemius: the biosynthesis of phenylalanine, tyrosine, and tryptophan; phenylalanine metabolism; histidine metabolism; and arginine and proline metabolism. In addition to phenylalanine-related pathways, lactate also plays a role in regulating branched-chain amino acid metabolism and energy metabolism. Notably, lactate treatment normalized the levels of eight essential metabolites in DMA mice, underscoring its potential as a therapeutic agent against the consequences of prolonged inactivity and muscle wasting. This study not only advances our understanding of the therapeutic benefits of lactate but also provides a foundation for novel treatment approaches aimed at metabolic restoration and muscle recovery in conditions of muscle wasting.
摘要：
废用性肌肉萎缩（DMA）是一项重要的医疗保健挑战，其特征在于长期不活动导致的肌肉质量和功能逐渐丧失。制定有效的肌肉恢复策略至关重要。在这项研究中,我们通过后肢悬吊建立了DMA小鼠模型，以评估乳酸在减轻对腓肠肌的有害影响方面的治疗潜力。使用基于NMR的代谢组学分析，我们调查了DMA损伤的腓肠肌与对照组相比的代谢变化,并评估了乳酸治疗的有益效果.我们的结果表明，乳酸通过下调Murf1表达显着减少肌肉质量损失并改善肌肉功能，减少蛋白质的泛素化和水解，和增加肌球蛋白重链水平。至关重要的是，乳酸校正了DMA腓肠肌四个关键代谢途径的扰动：苯丙氨酸的生物合成，酪氨酸,和色氨酸;苯丙氨酸代谢;组氨酸代谢;以及精氨酸和脯氨酸代谢。除了苯丙氨酸相关途径，乳酸还在调节支链氨基酸代谢和能量代谢中起作用。值得注意的是,乳酸处理使DMA小鼠中8种必需代谢物的水平正常化，强调其作为治疗剂对抗长期不活动和肌肉萎缩的后果的潜力。这项研究不仅促进了我们对乳酸的治疗益处的理解，而且还为旨在在肌肉萎缩的情况下进行代谢恢复和肌肉恢复的新型治疗方法提供了基础。
