Du Zhou, Lin Lisen, Li Yang, Sun Mengqi, Liang Qingqing, Sun Zhiwei, Duan Junchao
Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, China.
Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, China.
Free Radic Biol Med. 2022 Sep;190:16-27. doi: 10.1016/j.freeradbiomed.2022.07.024. Epub 2022 Aug 5.
Environmental fine particulate matter (PM), which has attracted worldwide attention, is associated with the progression of metabolic-associated fatty liver disease (MAFLD). However, it is unclear whether dietary habit exacerbate liver damage caused by PM. The current study aimed to investigate the combined negative effects of PM and high-fat diet (HFD) on liver lipid metabolism in C57BL/6J mice. Histopathological and Oil-Red O staining analysis illustrated that PM exposure resulted in increased liver fat content in HFD-fed C57BL/6J mice, but not in standard chow diet (STD)-fed mice. And there was a synergistic effect between PM and HFD on hepatic lipotoxicity. The increased ROS levels and augmented oxidative damage were evaluated in liver tissue of mice treated with PM and HFD together. In addition, excessive ROS production could activate the miR-155/peroxisome proliferator-activated receptor gamma (PPARγ) pathway, including up-regulation of lipid accumulation-related protein expressions of recombinant liver X receptor alpha (LXRα), sterol regulatory element binding protein-1 (SREBP-1), stearoyl-CoA desaturase-1 (SCD1), fatty acid synthase (FAS) and acetyl-CoA carboxylase 1 (ACC1).The use of miR-155 inhibitors demonstrated the indispensable role of miR-155 in the activation of lipid-regulated proteins by PM and palmitic acid (PA). Collectively, altering high-fat dietary habits could protect against MAFLD motivated by air pollution, and miR-155 might be an effective preventive and therapeutic target for this process.
环境细颗粒物（PM）已引起全球关注，它与代谢相关脂肪性肝病（MAFLD）的进展有关。然而，饮食习惯是否会加剧PM所致的肝损伤尚不清楚。当前研究旨在探究PM和高脂饮食（HFD）对C57BL/6J小鼠肝脏脂质代谢的联合负面影响。组织病理学和油红O染色分析表明，暴露于PM会导致高脂饮食喂养的C57BL/6J小鼠肝脏脂肪含量增加，但对标准饲料（STD）喂养的小鼠没有影响。并且PM和HFD对肝脏脂毒性存在协同作用。对同时用PM和HFD处理的小鼠肝脏组织评估了升高的活性氧（ROS）水平和增强的氧化损伤。此外，过量的ROS产生可激活miR-155/过氧化物酶体增殖物激活受体γ（PPARγ）途径，包括上调重组肝X受体α（LXRα）、固醇调节元件结合蛋白-1（SREBP-1）、硬脂酰辅酶A去饱和酶-1（SCD1）、脂肪酸合酶（FAS）和乙酰辅酶A羧化酶1（ACC1）等脂质积累相关蛋白的表达。使用miR-155抑制剂证明了miR-155在PM和棕榈酸（PA）激活脂质调节蛋白中的不可或缺作用。总体而言，改变高脂饮食习惯可预防空气污染引发的MAFLD，而miR-155可能是这一过程有效的预防和治疗靶点。
