Lipid metabolic disruption: A potential mechanistic pathway for 2,4,6-tribromophenol-induced neurotoxicity in zebrafish

  • Environ Int. 2026 Jul:213:110355. doi: 10.1016/j.envint.2026.110355.
Yumiao Sun  1 ,  Yindan Zhang  2 ,  Tianyan Guan  3 ,  Xiaoxi Yang  4 ,  Qian S Liu  4 ,  Bingsheng Zhou  5 ,  Li Xu  6 ,  Qunfang Zhou  7 ,  Guibin Jiang  8
Affiliations
  • 1. Institute of Quality Standard and Testing Technology, Beijing Academy of Agriculture and Forestry Sciences, Beijing 100097, China; State Key Laboratory of Environmental Chemistry and Toxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.
  • 2. Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China; College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100049, China.
  • 3. College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100049, China; School of Environment, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China.
  • 4. State Key Laboratory of Environmental Chemistry and Toxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.
  • 5. Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China.
  • 6. Institute of Quality Standard and Testing Technology, Beijing Academy of Agriculture and Forestry Sciences, Beijing 100097, China. Electronic address: [email protected].
  • 7. State Key Laboratory of Environmental Chemistry and Toxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100049, China; School of Environment, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China; Institute of Environment and Health, Jianghan University, Wuhan 430056, China. Electronic address: [email protected].
  • 8. State Key Laboratory of Environmental Chemistry and Toxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100049, China; School of Environment, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China.
PMID: 42288112 DOI: 10.1016/j.envint.2026.110355
Abstract

2,4,6-Tribromophenol (TBP) is a widespread emerging environmental pollutant that tends to accumulate in the brain. Growing evidence implicates disrupted brain lipid homeostasis in contaminant-induced neurotoxicity. To explore this potential link, we investigated the neurotoxic and lipid-disrupting effects of TBP using zebrafish larvae. Multi-level neurotoxicity assessment in whole larvae showed that TBP exposure induced concentration-dependent decreases in locomotor activity and a trend toward anxiety-like behaviors. Moreover, TBP significantly altered neuronal differentiation. At the neurochemical level, neurotransmitter homeostasis was disrupted, specifically marked by decreases in the levels of acetylcholine, serotonin, and epinephrine. Concomitantly, TBP induced a systemic lipid dysregulation, characterized by elevated total Cholesterol and reduced triglyceride levels. Region-specific alterations were evident: abnormal neutral lipid accumulation occurred in the yolk sac, while lipid levels in the head region exhibited significant reductions. The transcripts of lipid metabolism genes in whole larvae were widely suppressed. To explore the correlation between lipid dysregulation and neurotoxicity, a rescue experiment was conducted using the liver X receptor (LXR) agonist GW3965. LXR activation restored the gene expression of systemic lipid transport and normalized head lipid levels. Notably, this restoration of lipid homeostasis partially alleviated the TBP-induced neurotransmitter deficits. Collectively, these results suggest that TBP exposure may impair neurodevelopment and function, and support lipid metabolic disruption as a potential mechanistic link underlying the consequent neurotoxicity. Our findings provide a preliminary mechanistic basis for evaluating the neurotoxic potential of Other emerging environmental contaminants with metabolism-disrupting properties.

Keywords
2,4,6-tribromophenol; Developmental neurotoxicity; Lipid metabolism; Liver X receptor; Neurotransmitter; Zebrafish larvae.
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