Wang Yu, Sun Juan, Xue Lamei, Sun Yujie, Zhang Kuiliang, Fan Mingcong, Qian Haifeng, Li Yan, Wang Li
State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi 214122, China.
J Agric Food Chem. 2025 Apr 30;73(17):10347-10357. doi: 10.1021/acs.jafc.5c03967. Epub 2025 Apr 15.
Mitochondria are pivotal in sustaining skeletal muscle and the systemic metabolic balance. Chlorogenic acid (CA) is a common dietary antioxidant known for its ability to modulate metabolic homeostasis. This study aimed to investigate the impact of CA on high-fat diet (HFD)-induced mitochondrial dysfunction and metabolic disorder in skeletal muscle. C57BL/6J mice fed with a HFD were treated with CA for 12 weeks. The study assessed the overall glycolipid metabolic status, exercise performance, muscle fiber type, and antioxidant capacity of skeletal muscle in HFD-fed mice treated with CA. Results showed that CA reduced fat accumulation, improved exercise capacity, and enhanced mitochondrial performance in HFD-fed mice. Untargeted metabolomics analysis revealed that lactate metabolism and mitochondrial fatty acid oxidation (FAO) responded positively to CA intervention. Molecular mechanisms demonstrated that CA intervention improved mitochondrial biogenesis and function, promoting FAO and oxidative phosphorylation in mitochondria and ultimately reducing fat deposition in skeletal muscle induced by HFD feeding. Mechanistically, CA decreased HFD-induced lactate production and protein lactylation in skeletal muscle, highlighting the importance of the LDHA-lactate axis in mitochondrial function improvement by CA. Therefore, this study provides additional insights supporting the potential of CA as a natural dietary supplement for metabolic syndrome and associated disorders.
线粒体在维持骨骼肌和全身代谢平衡方面起着关键作用。绿原酸（CA）是一种常见的膳食抗氧化剂，以其调节代谢稳态的能力而闻名。本研究旨在探讨CA对高脂饮食（HFD）诱导的骨骼肌线粒体功能障碍和代谢紊乱的影响。给喂食HFD的C57BL/6J小鼠用CA治疗12周。该研究评估了用CA治疗的HFD喂养小鼠的总体糖脂代谢状况、运动能力、肌纤维类型和骨骼肌的抗氧化能力。结果表明，CA减少了HFD喂养小鼠的脂肪堆积，提高了运动能力，并增强了线粒体性能。非靶向代谢组学分析表明，乳酸代谢和线粒体脂肪酸氧化（FAO）对CA干预有积极反应。分子机制表明，CA干预改善了线粒体生物发生和功能，促进了线粒体中的FAO和氧化磷酸化，并最终减少了HFD喂养诱导的骨骼肌脂肪沉积。从机制上讲，CA降低了HFD诱导的骨骼肌乳酸产生和蛋白质乳酸化，突出了LDHA-乳酸轴在CA改善线粒体功能中的重要性。因此，本研究提供了更多见解，支持CA作为代谢综合征及相关疾病的天然膳食补充剂的潜力。
