Long-term low-dose exposure to 9-chlorophenanthrene induces liver lipid accumulation via disrupting circadian rhythm

  • J Hazard Mater. 2025 Sep 5:495:139145. doi: 10.1016/j.jhazmat.2025.139145.
Meitong Liu  1 ,  Yaqi Lu  2 ,  Hongjiang Zhou  1 ,  Yuelin Chen  1 ,  Yang Li  3 ,  Tiehua Zhang  4
Affiliations
  • 1. College of Food Science and Engineering, Jilin University, Changchun, Jilin 130062, China.
  • 2. College of Food science and Engineering, Northeast Agricultural University, Harbin, Heilongjiang 150030, China.
  • 3. College of Food Science and Engineering, Jilin University, Changchun, Jilin 130062, China; College of Food science and Engineering, Northeast Agricultural University, Harbin, Heilongjiang 150030, China; Heilongjiang Province China-Mongolia-Russia Joint R&D Laboratory for Bio-processing and Equipment for Agricultural Products (International Cooperation), Department of Food Science, Northeast Agricultural University, Harbin 150030, China. Electronic address: [email protected].
  • 4. College of Food Science and Engineering, Jilin University, Changchun, Jilin 130062, China. Electronic address: [email protected].
PMID: 40628211 DOI: 10.1016/j.jhazmat.2025.139145
Abstract

9-Chlorophenanthrene (9-ClPhe) is the most widely distributed chlorinated polycyclic aromatic hydrocarbons (ClPAHs) in environmental matrices such as the atmosphere, aquatic environments. However, the long-term low-dose toxicity of 9-ClPhe remains unclear. This study aimed to elucidate the effects and underlying mechanisms of 9-ClPhe on hepatic lipid accumulation and circadian rhythm disruption in C57BL/6 mice following a 90-day continuous exposure. Utilizing histopathological analyses and biochemical assays, we demonstrated that exposure to low-dose 9-ClPhe resulted in significant lipid accumulation in the liver. Peroxisome Proliferator-activated Receptor α (PPARα) activator (WY14643) was found to attenuate this hepatic lipid accumulation, indicating a critical role for PPARα in mitigating 9-ClPhe-induced effects. Moreover, our findings showed that 9-ClPhe reduced brain and muscle arnt-like protein 1 (BMAL1) protein expression, pivotal for PPARα activation, while melatonin administration restored BMAL1 levels, thereby alleviating lipid accumulation. Notably, co-immunoprecipitation assays revealed a binding interaction between Aryl Hydrocarbon Receptor (AHR) and BMAL1, suggesting that 9-ClPhe activated AHR, leading to its interaction with BMAL1 and circadian disruption. Meanwhile, treatment with the AHR inhibitor (CH223191) mitigated 9-ClPhe-induced lipid accumulation and circadian disturbances. Collectively, our findings demonstrated that chronic low-dose 9-ClPhe exposure promoted hepatic lipid accumulation by activating the AHR-BMAL1 interaction, leading to circadian perturbation. These results highlighted the potential of low-dose 9-ClPhe to drive lipid accunmulation through circadian disruption.

Keywords
9-ClPhe; Circadian rhythm; ClPAHs; Lipid accumulation.
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