Yan Zhipeng, Li Shuyue, Chen Rui, Xie Haohan, Wu Meiqiong, Nan Nan, Xing Qisong, Yun Yang, Qin Guohua, Sang Nan
College of Environment and Resource, Research Center of Environment and Health, Shanxi University, Shanxi, 030006, PR China.
Beijing Key Laboratory of Occupational Safety and Health, Institute of Urban Safety and Environmental Science, Beijing Academy of Science and Technology, Beijing, 100054, PR China; Beijing City University, Beijing, 11418, PR China.
Environ Pollut. 2023 Apr 15;323:121220. doi: 10.1016/j.envpol.2023.121220. Epub 2023 Feb 4.
Emerging evidence suggests that exposure to PM is associated with a high risk of nonalcoholic fatty liver disease (NAFLD). NAFLD is typically characterised by hepatic steatosis. However, the underlying mechanisms and critical components of PM-induced hepatic steatosis remain to be elucidated. In this study, ten-month-old C57BL/6 female mice were exposed to PM from four cities in China (Taiyuan, Beijing, Hangzhou, and Guangzhou) via oropharyngeal aspiration every other day for four weeks. After the exposure period, hepatic lipid accumulation was evaluated by biochemical and histopathological analyses. The expression levels of genes related to lipid metabolism and metabolomic profiles were assessed in the mouse liver. The association between biomarkers of hepatic steatosis (hepatic Oil Red O staining area and serum and liver triglyceride contents) and typical components of PM was identified using Pearson correlation analysis. Oil Red O staining and biochemical results indicated that PM from four cities significantly induced hepatic lipid accumulation. The most severe hepatic steatosis was observed after Guangzhou PM exposure. Moreover, Guangzhou PM-induced the most significant changes in gene expression associated with lipid metabolism, including increased hepatic fatty acid uptake and lipid droplet formation and decreased fatty acid synthesis and lipoprotein secretion. Contemporaneously, exposure to Guangzhou PM significantly perturbed hepatic lipid metabolism. According to metabolomic analysis, disturbed hepatic lipid metabolism was primarily concentrated in linoleic acid, α-linoleic acid, and arachidonic acid metabolism. Finally, correlation analysis revealed that copper (Cu) and other inorganic components, as well as the majority of polycyclic aromatic hydrocarbons (PAHs), were related to changes in biomarkers of hepatic steatosis. These findings showed that PM exposure caused hepatic steatosis in aged mice, which could be related to the critical chemical components of PM. This study provides critical information regarding the components of PM, which cause hepatic steatosis.
新出现的证据表明，接触细颗粒物（PM）与非酒精性脂肪性肝病（NAFLD）的高风险相关。NAFLD通常以肝脂肪变性为特征。然而，PM诱导肝脂肪变性的潜在机制和关键成分仍有待阐明。在本研究中，对10月龄的C57BL/6雌性小鼠每隔一天通过口咽吸入法暴露于来自中国四个城市（太原、北京、杭州和广州）的PM中，持续四周。暴露期结束后，通过生化和组织病理学分析评估肝脏脂质蓄积情况。在小鼠肝脏中评估与脂质代谢相关的基因表达水平和代谢组学谱。使用Pearson相关分析确定肝脂肪变性生物标志物（肝脏油红O染色面积以及血清和肝脏甘油三酯含量）与PM典型成分之间的关联。油红O染色和生化结果表明，来自四个城市的PM均显著诱导肝脏脂质蓄积。在暴露于广州PM后观察到最严重的肝脂肪变性。此外，广州PM诱导的与脂质代谢相关的基因表达变化最为显著，包括肝脏脂肪酸摄取增加和脂滴形成增加，以及脂肪酸合成和脂蛋白分泌减少。同时，暴露于广州PM显著扰乱了肝脏脂质代谢。根据代谢组学分析，肝脏脂质代谢紊乱主要集中在亚油酸、α-亚麻酸和花生四烯酸代谢方面。最后，相关分析显示，铜（Cu）和其他无机成分以及大多数多环芳烃（PAHs）与肝脂肪变性生物标志物的变化有关。这些发现表明，暴露于PM会导致老年小鼠发生肝脂肪变性，这可能与PM的关键化学成分有关。本研究提供了关于导致肝脂肪变性的PM成分的关键信息。
