Wang Yu, Wang Feijie, Sun Juan, Xue Lamei, Sun Yujie, Zhang Kuiliang, Fan Mingcong, Qian Haifeng, Yang Binrui, Du Jun, Li Yan, Wang Li
State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, China.
Nutrilite Health Institute, Shanghai, China.
Mol Nutr Food Res. 2025 Aug;69(16):e70106. doi: 10.1002/mnfr.70106. Epub 2025 Jun 9.
Obesity-induced mitochondrial dysfunction impairs skeletal muscle metabolic flexibility. Gallic acid possesses the ability to modulate metabolic homeostasis. This study aimed to investigate the impact of gallic acid on high-fat diet (HFD)-induced metabolic disorders in skeletal muscle. Twenty-four mice were randomly divided into three groups and subjected to HFD and gallic acid intervention for 12 weeks. The overall glycolipid metabolic status, exercise performance, muscle fiber type, and antioxidant capacity of skeletal muscle in HFD-fed mice treated with gallic acid were assessed. Untargeted metabolomics analysis was performed to evaluate key metabolic characteristics in skeletal muscle. Gallic acid administration effectively reduced fat accumulation, improved exercise capacity, and enhanced antioxidant capacity in HFD-fed mice. Untargeted metabolomics revealed that gallic acid positively regulated lactate metabolism and mitochondrial fatty acid oxidation. Mechanistically, gallic acid intervention increased fatty acid oxidation capacity while inhibiting lactate production and mitochondrial protein lactylation in skeletal muscle. Moreover, the role of gallic acid in enhancing mitochondrial function through the LDHA-lactate axis has been demonstrated in C2C12 cells. Collectively, gallic acid ameliorated HFD-induced metabolic disorders in skeletal muscle, indicating a novel role for gallic acid in ameliorating diet-induced skeletal muscle metabolic disorders by regulating lactate metabolism and mitochondrial function.
肥胖诱导的线粒体功能障碍损害骨骼肌代谢灵活性。没食子酸具有调节代谢稳态的能力。本研究旨在探讨没食子酸对高脂饮食（HFD）诱导的骨骼肌代谢紊乱的影响。将24只小鼠随机分为三组，进行12周的高脂饮食和没食子酸干预。评估了用没食子酸处理的高脂饮食喂养小鼠骨骼肌的整体糖脂代谢状态、运动能力、肌纤维类型和抗氧化能力。进行非靶向代谢组学分析以评估骨骼肌中的关键代谢特征。给予没食子酸有效减少了高脂饮食喂养小鼠的脂肪堆积，改善了运动能力，并增强了抗氧化能力。非靶向代谢组学显示没食子酸对乳酸代谢和线粒体脂肪酸氧化具有正向调节作用。机制上，没食子酸干预增加了脂肪酸氧化能力，同时抑制了骨骼肌中的乳酸产生和线粒体蛋白乳酸化。此外，在C2C12细胞中已证明没食子酸通过LDHA-乳酸轴增强线粒体功能的作用。总体而言，没食子酸改善了高脂饮食诱导的骨骼肌代谢紊乱，表明没食子酸在通过调节乳酸代谢和线粒体功能改善饮食诱导的骨骼肌代谢紊乱方面具有新作用。
