School of Basic Medical Sciences and Public Health, Joint China-US Research Center for Environment and Pulmonary Diseases, Zhejiang Chinese Medical University, Hangzhou 310053, China.
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, Beijing Key Laboratory of Ambient Particles Health Effects and Prevention Techniques, National Center for Nanoscience and Technology of China and University of Chinese Academy of Sciences, Beijing 100190, China; Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, College of Chemistry and Environmental Science, Hebei University, Baoding, China.
Environ Pollut. 2020 Jul;262:114179. doi: 10.1016/j.envpol.2020.114179. Epub 2020 Feb 28.
Emerging evidence has shown that exposure to ambient fine particulate matter (PM) is associated with hepatic lipid accumulation. However, the underlying mechanism is not fully characterized yet. Autonomous circadian clock in the liver plays a fundamental role in maintaining lipid metabolism homeostasis. In this study, we evaluated the effects of ambient PM exposure on the expression of hepatic circadian clock genes and expression rhythm of genes associated with lipid metabolism in mice liver. Male C57BL/6 mice were randomly assigned to ambient PM or filtered air for 10 weeks via a whole body exposure system. We found that the liver mass was reduced significantly at zeitgeber time (ZT) 8 in mice exposed to PM but not levels or circadian rhythm of hepatic triglycerides or free fatty acid (FFA). In addition, exposure to PM led to enhanced expression of bmal1 at ZT0/24, cry1 at ZT16 and rev-erbα at ZT4 and ZT8. Furthermore, the expression of pparα was enhanced in mice liver at ZT4 and ZT8 after PM exposure, with upregulation of pparα-mediated genes responsible for fatty acid transport and oxidation. Finally, the expression of rate-limiting enzymes for lipid synthesis was all significantly increased in the liver of PM exposed mice at ZT12. Therefore, the present study provides new perspectives for revealing the etiology of hepatic lipid metabolism abnormality from PM-induced circadian rhythm disorder.
新兴证据表明，暴露于环境细颗粒物（PM）与肝内脂质积累有关。然而，其潜在机制尚未完全阐明。肝脏中的自主生物钟在维持脂质代谢平衡方面起着至关重要的作用。在这项研究中，我们评估了环境 PM 暴露对小鼠肝脏生物钟基因表达和与脂质代谢相关基因表达节律的影响。雄性 C57BL/6 小鼠通过全身暴露系统随机分配到环境 PM 或过滤空气中 10 周。我们发现，暴露于 PM 的小鼠在 Zeitgeber 时间（ZT）8 时肝脏质量显著降低，但肝三酰甘油或游离脂肪酸（FFA）水平或昼夜节律不受影响。此外，PM 暴露导致 bmal1 在 ZT0/24 时、cry1 在 ZT16 时和 rev-erbα在 ZT4 和 ZT8 时表达增强。此外，PPARα 在 PM 暴露后的小鼠肝脏中在 ZT4 和 ZT8 时增强表达，与脂肪酸转运和氧化相关的 pparα 介导基因上调。最后，PM 暴露小鼠肝脏中脂质合成限速酶的表达在 ZT12 时均显著增加。因此，本研究为揭示 PM 诱导的昼夜节律紊乱导致肝脂质代谢异常的病因提供了新的视角。
