Jiang Jin-Jin, Zhang Guo-Fu, Zheng Jia-Yi, Sun Ji-Hu, Ding Shi-Bin
Jiangsu Vocational College of Medicine, Yancheng, China.
Department of Public Health, Xinxiang Medical University, Xinxiang, China.
Front Pharmacol. 2022 Apr 12;13:876550. doi: 10.3389/fphar.2022.876550. eCollection 2022.
The protective effect of quercetin on nonalcoholic fatty liver disease (NAFLD) has been reported, but its mechanism remains poorly understood. Recently, quercetin was reported to be capable of inhibiting ferroptosis, which is a recognized type of regulated cell death. Moreover, hepatic ferroptosis plays an important role in the progression of NAFLD, but experimental evidence is limited. Hence, our study aimed to investigate the effect of quercetin on hepatic ferroptosis in high-fat diet (HFD)-induced NAFLD and further elucidate the underlying molecular mechanism. C57BL/6J mice were fed either a normal diet (ND), an HFD, or an HFD supplemented with quercetin for 12 weeks. Hepatic lipid peroxidation, steatosis, ferroptosis and iron overload were examined. , steatotic L-02 cells was used to study the potential mechanism. We found that the HFD caused lipid peroxidation, lipid accumulation and ferroptosis in the liver, which were rescued by quercetin supplementation. Consistent with the results, quercetin alleviated lipid droplet accumulation and reduced the levels of lipid reactive oxygen species (ROS) and ferroptosis in steatotic L-02 cells. Using a mitochondrial ROS (MtROS) scavenger (Mito-TEMPO) and ferroptosis specific inhibitor (Fer-1), we found that quercetin remarkably alleviated lipid droplet accumulation and lipid peroxidation by reducing MtROS-mediated ferroptosis in steatotic L-02 cells. Our data showed that HFD consumption induced lipid accumulation and triggered ferroptosis in liver, ultimately leading to hepatic lipotoxicity, which can be alleviated by quercetin. Findings from this study provide new insight into the mechanism by which quercetin can be used for the prevention and treatment of NAFLD.
槲皮素对非酒精性脂肪性肝病（NAFLD）的保护作用已有报道，但其机制仍不清楚。最近，有报道称槲皮素能够抑制铁死亡，这是一种公认的程序性细胞死亡类型。此外，肝脏铁死亡在NAFLD的进展中起重要作用，但实验证据有限。因此，我们的研究旨在探讨槲皮素对高脂饮食（HFD）诱导的NAFLD肝脏铁死亡的影响，并进一步阐明其潜在的分子机制。将C57BL/6J小鼠分为正常饮食（ND）组、HFD组或补充槲皮素的HFD组，喂养12周。检测肝脏脂质过氧化、脂肪变性、铁死亡和铁过载情况。此外，利用脂肪变性的L-02细胞研究潜在机制。我们发现，HFD导致肝脏脂质过氧化、脂质蓄积和铁死亡，补充槲皮素可使其得到缓解。与上述结果一致，槲皮素减轻了脂肪变性的L-02细胞中脂滴的积累，并降低了脂质活性氧（ROS）水平和铁死亡。使用线粒体ROS（MtROS）清除剂（Mito-TEMPO）和铁死亡特异性抑制剂（Fer-1），我们发现槲皮素通过减少MtROS介导的脂肪变性L-02细胞铁死亡，显著减轻了脂滴积累和脂质过氧化。我们的数据表明，食用HFD会诱导肝脏脂质蓄积并引发铁死亡，最终导致肝脏脂毒性，而槲皮素可以缓解这种情况。本研究结果为槲皮素用于预防和治疗NAFLD的机制提供了新见解。
