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.
Chemosphere. 2020 Jul;251:126392. doi: 10.1016/j.chemosphere.2020.126392. Epub 2020 Feb 29.
Emerging evidence indicated that disruption of circadian rhythm (CR) induced metabolic disorders, including dysregulation of energy homeostasis and lipid dysfunction, which was associated with ambient fine particulate matter (PM) as well. However, the role and mechanism of CR in PM-mediated metabolic disorder remain unknown. In the present study, we investigated circadian rhythmic characteristics and explored the effect of PM on oscillating clock of lipid function and metabolism in white adipose tissue (WAT) and brown adipose tissue (BAT). C57BL/6 mice were exposed to PM in a whole-body inhalational exposure system. After 10 weeks, the expression of clock-related genes exhibits more robust CR in BAT than WAT, with the acrophase of PER2 in both types of adipose tissue being significantly decreased at ZT12 and Bmal1 increased at ZT0/24 in WAT in response to PM exposure. In addition, both CR pattern and expression levels of Sirt1 got significantly inhibited by PM exposure in WAT, accompanied with adipose dysfunction evidenced by inhibited pattern and expression levels of adipokines at the same ZT time points. Finally, a similar phase right shift from ZT4 to ZT12 in both Sirt3 and Ucp1 in BAT was induced by PM exposure. These findings indicate that disruption of the CR in adipose tissues could be an important way by which PM exposure induces metabolic disorder and provide potential targets for further investigation.
新兴证据表明,昼夜节律(CR)的破坏会导致代谢紊乱,包括能量平衡和脂质功能失调的调节异常,这也与环境细颗粒物(PM)有关。然而,CR 在 PM 介导的代谢紊乱中的作用和机制尚不清楚。在本研究中,我们研究了昼夜节律的特征,并探讨了 PM 对白色脂肪组织(WAT)和棕色脂肪组织(BAT)中脂质功能和代谢振荡时钟的影响。C57BL/6 小鼠在全身吸入暴露系统中暴露于 PM。10 周后,与 WAT 相比,BAT 中的时钟相关基因的表达表现出更强的 CR,两种脂肪组织中 PER2 的峰值在 ZT12 时明显降低,Bmal1 在 WAT 中在 ZT0/24 时增加,以响应 PM 暴露。此外,PM 暴露在 WAT 中显著抑制了 CR 模式和 Sirt1 的表达水平,同时在相同的 ZT 时间点,脂肪细胞因子的表达模式和水平也受到抑制,表明脂肪功能障碍。最后,PM 暴露诱导 BAT 中 Sirt3 和 Ucp1 的相似相位从 ZT4 右移到 ZT12。这些发现表明,脂肪组织中 CR 的破坏可能是 PM 暴露诱导代谢紊乱的重要途径,并为进一步研究提供了潜在的靶点。