Ambient fine particulate matter disrupts hepatic circadian oscillation and lipid metabolism in a mouse model

Li, Ran; Wang, Yixuan; Chen, Rucheng; Gu, Weijia; Zhang, Lu; Gu, Jincui; Wang, Ziyao; Liu, Ying; Sun, Qinghua; Zhang, Kezhong; Liu, Cuiqing

doi:10.1016/j.envpol.2020.114179

Cited by 44 publications

(21 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Overall, our data suggest that PM 2.5 is comparable with light exposure in causing widespread circadian disruption in the liver and BAT. Our results on circadian gene variations in liver and BAT are different from those recently published (Li et al, 2020;Wang et al, 2020). This could be due to the duration of PM 2.5 exposure (10 versus 30 weeks in our study, which truly represents a chronic exposure scenario), inclusion of light at night as a positive control comparator, and the unbiased nature of our analysis.…”

Section: Ll Open Accesscontrasting

confidence: 97%

Exposure to Air Pollution Disrupts Circadian Rhythm through Alterations in Chromatin Dynamics

et al. 2020

View full text Add to dashboard Cite

Summary Particulate matter ≤2.5μm (PM 2.5 ) air pollution is a leading environmental risk factor contributing disproportionately to the global burden of non-communicable disease. We compared impact of chronic exposure to PM 2.5 alone, or with light at night exposure (LL) on metabolism. PM 2.5 induced peripheral insulin resistance, circadian rhythm (CR) dysfunction, and metabolic and brown adipose tissue (BAT) dysfunction, akin to LL (with no additive interaction between PM 2.5 and LL). Transcriptomic analysis of liver and BAT revealed widespread but unique alterations in CR genes, with evidence for differentially accessible promoters and enhancers of CR genes in response to PM 2.5 by ATAC-seq. The histone deacetylases 2, 3, and 4 were downregulated with PM 2.5 exposure, with increased promoter occupancy by the histone acetyltransferase p300 as evidenced by ChIP-seq. These findings suggest a previously unrecognized role of PM 2.5 in promoting CR disruption and metabolic dysfunction through epigenetic regulation of circadian targets.

show abstract

Section: Ll Open Accesscontrasting

confidence: 97%

Exposure to Air Pollution Disrupts Circadian Rhythm through Alterations in Chromatin Dynamics

et al. 2020

View full text Add to dashboard Cite

show abstract

“…The harmful effect triggered by PM includes the oxidative stress mechanism, which can regulate the pathogenesis of inflammation in various organs [ 15 , 22 , 47 , 48 ]. The signaling pathways through which PM 2.5 exposure promotes hepatic dysfunction and impairments of hepatic lipid/glucose metabolism have been widely revealed [ [8] , [9] , [10] , 23 ]. However, the pronounced effect of PM 2.5 exposure on the meditation of hepatic pathways associated with oxidative stress and inflammation has not been fully characterized.…”

Section: Discussionmentioning

confidence: 99%

“…PM 2.5 can directly enter the circulatory system, influencing the function of body tissues and organs, including liver [ 6 , 7 ]. Epidemiological study suggests that PM 2.5 pollution may be a risk factor for the increase in the incidence of liver injury worldwide, and liver is the main organ for metabolism and detoxification [ 8 , 9 ]. In rodent animals, the whole-body exposure to concentrated ambient PM 2.5 results in a nonalcoholic steatohepatitis (NASH)-like phenotype [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Nrf2 mitigates prolonged PM2.5 exposure-triggered liver inflammation by positively regulating SIKE activity: Protection by Juglanin

Ge¹,

Tan

Zhong

et al. 2020

Redox Biology

View full text Add to dashboard Cite

Air pollution containing particulate matter (PM) less than 2.5 μm (PM 2.5 ) plays an essential role in regulating hepatic disease. However, its molecular mechanism is not yet clear, lacking effective therapeutic strategies. In this study, we attempted to investigate the effects and mechanisms of PM 2.5 exposure on hepatic injury by the in vitro and in vivo experiments. At first, we found that PM 2.5 incubation led to a significant reduction of nuclear factor erythroid-derived 2-related factor 2 (Nrf2), along with markedly reduced expression of different anti-oxidants. Notably, suppressor of IKKε (SIKE), known as a negative regulator of the interferon pathway, was decreased in PM 2.5 -incubated cells, accompanied with increased activation of TANK-binding kinase 1 (TBK1) and nuclear factor-κB (NF-κB). The in vitro studies showed that Nrf2 positively regulated SIKE expression under the conditions with or without PM 2.5 . After PM 2.5 treatment, Nrf2 knockdown further accelerated SIEK decrease and TBK1/NF-κB activation, and opposite results were observed in cells with Nrf2 over-expression. Subsequently, the gene loss- and gain-function analysis demonstrated that SIKE deficiency further aggravated inflammation and TBK1/NF-κB activation caused by PM 2.5 , which could be abrogated by SIKE over-expression. Importantly, SIKE-alleviated inflammation was mainly dependent on TBK1 activation. The in vivo studies confirmed that SIKE- and Nrf2-knockout mice showed significantly accelerated hepatic injury after long-term PM 2.5 exposure through reducing inflammatory response and oxidative stress. Juglanin (Jug), mainly isolated from Polygonum aviculare , exhibits anti-inflammatory and anti-oxidant effects. We found that Jug could increase Nrf2 activation, and then up-regulated SIKE in cells and liver tissues, mitigating PM 2.5 -induced liver injury. Together, all these data demonstrated that Nrf2 might positively meditate SIKE to inhibit inflammatory and oxidative damage, ameliorating PM 2.5 -induced liver injury. Jug could be considered as an effective therapeutic strategy against this disease by improving Nrf2/SIKE signaling pathway.

show abstract

“… 247 , 250 Furthermore, circadian disruption is associated with obesity, 82 , 83 and PM exposure can perturb circadian rhythms. 141 , 242 Developing strategies to investigate these factors separately and in tandem could help determine if there is a synergistic effect or if both risk factors increase vulnerability through similar mechanisms. Furthermore, PM exposure and circadian rhythm disruption could impact cytokine release, and additional studies are needed to confirm the mechanism through which this occurs and the implications for COVID-19 treatment.…”

Section: Discussionmentioning

confidence: 99%

Significant Unresolved Questions and Opportunities for Bioengineering in Understanding and Treating COVID-19 Disease Progression

et al. 2020

View full text Add to dashboard Cite

COVID-19 is a disease that manifests itself in a multitude of ways across a wide range of tissues. Many factors are involved, and though impressive strides have been made in studying this novel disease in a very short time, there is still a great deal that is unknown about how the virus functions. Clinical data has been crucial for providing information on COVID-19 progression and determining risk factors. However, the mechanisms leading to the multi-tissue pathology are yet to be fully established. Although insights from SARS-CoV-1 and MERS-CoV have been valuable, it is clear that SARS-CoV-2 is different and merits its own extensive studies. In this review, we highlight unresolved questions surrounding this virus including the temporal immune dynamics, infection of non-pulmonary tissue, early life exposure, and the role of circadian rhythms. Risk factors such as sex and exposure to pollutants are also explored followed by a discussion of ways in which bioengineering approaches can be employed to help understand COVID-19. The use of sophisticated in vitro models can be employed to interrogate intercellular interactions and also to tease apart effects of the virus itself from the resulting immune response. Additionally, spatiotemporal information can be gleaned from these models to learn more about the dynamics of the virus and COVID-19 progression. Application of advanced tissue and organ system models into COVID-19 research can result in more nuanced insight into the mechanisms underlying this condition and elucidate strategies to combat its effects.

show abstract

Ambient fine particulate matter disrupts hepatic circadian oscillation and lipid metabolism in a mouse model

Cited by 44 publications

References 23 publications

Exposure to Air Pollution Disrupts Circadian Rhythm through Alterations in Chromatin Dynamics

Exposure to Air Pollution Disrupts Circadian Rhythm through Alterations in Chromatin Dynamics

Nrf2 mitigates prolonged PM2.5 exposure-triggered liver inflammation by positively regulating SIKE activity: Protection by Juglanin

Significant Unresolved Questions and Opportunities for Bioengineering in Understanding and Treating COVID-19 Disease Progression

Contact Info

Product

Resources

About