Xu Liancheng, Li Wenwen, Chen Yu, Liu Shan, Liu Guodong, Luo Weihuan, Cao Guanyi, Wang Shiping
Department of General Surgery, Suqian First Hospital, No.120 Suzhi Street, Suqian, 223800, Jiangsu Province, China.
Fujian Medical University, Fuzhou, 350108, China.
Appl Biochem Biotechnol. 2025 Jan;197(1):179-193. doi: 10.1007/s12010-024-05038-7. Epub 2024 Aug 6.
High-fat diet-induced metabolic syndrome (MetS) is closely associated with cardiac dysfunction. Recent research studies have indicated a potential association between MetS and ferroptosis. Furthermore, metformin can alleviate MetS-induced cardiac ferroptosis. Metformin is a classic biguanide anti-diabetic drug that has protective effects on cardiovascular diseases, which extend beyond its indirect glycemic control. This study aimed to assess whether MetS mediates cardiac ferroptosis, thereby causing oxidative stress and mitochondrial dysfunction. The results revealed that metformin can mitigate cardiac reactive oxygen species and mitochondrial damage, thereby preserving cardiac function. Mechanistic analysis revealed that metformin upregulates the expression of cardiac Nrf2. Moreover, Nrf2 downregulation compromises the cardio-protective effects of metformin. In summary, this study indicated that MetS promotes cardiac ferroptosis, and metformin plays a preventive and therapeutic role, partially through modulation of Nrf2 expression.
高脂饮食诱导的代谢综合征（MetS）与心脏功能障碍密切相关。最近的研究表明MetS与铁死亡之间存在潜在关联。此外，二甲双胍可以减轻MetS诱导的心脏铁死亡。二甲双胍是一种经典的双胍类抗糖尿病药物，对心血管疾病具有保护作用，这种作用超出了其间接控制血糖的范围。本研究旨在评估MetS是否介导心脏铁死亡，从而导致氧化应激和线粒体功能障碍。结果显示，二甲双胍可以减轻心脏活性氧和线粒体损伤，从而保护心脏功能。机制分析表明，二甲双胍上调心脏Nrf2的表达。此外，Nrf2的下调会损害二甲双胍的心脏保护作用。总之，本研究表明MetS促进心脏铁死亡，而二甲双胍发挥预防和治疗作用，部分是通过调节Nrf2的表达来实现的。
