小児の尿中有機リン系殺虫剤代謝物濃度は血中コレステロール濃度高値と関連する~有機リン系殺虫剤が肝臓の脂質代謝を変化させる可能性を示唆~

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2025-12-04 東京科学大学

東京科学大学と国立環境研究所らの研究チームは、米国NHANESに参加した6~11歳の小児385名のデータを用い、尿中有機リン系殺虫剤代謝物(DAP)と血中脂質との関連を解析した。その結果、DAPの一種DETP濃度が最も高い群は、最も低い群に比べ総コレステロール≧200 mg/dLとなるオッズ比が4.35と有意に高く、LDLコレステロールでも同様の傾向が見られた。一方HDLや中性脂肪との関連は明確でなかった。さらに、フェンチオン曝露マウス肝臓のRNAシーケンス解析から、PPARα・PPARγ標的遺伝子の発現亢進が確認され、有機リン系殺虫剤が肝臓脂質代謝を変化させ、小児の脂質異常症リスクを高める可能性が示唆された。ただし因果関係は未解明で、今後の追跡研究が必要である。

小児の尿中有機リン系殺虫剤代謝物濃度は血中コレステロール濃度高値と関連する~有機リン系殺虫剤が肝臓の脂質代謝を変化させる可能性を示唆~
図1.本研究で検証した関連性

<関連情報>

米国の子供の尿中有機リン系農薬代謝物と血中脂質濃度の関連性 Association between urinary organophosphate pesticide metabolites and blood lipid levels in US children

Nobuhisa Morimoto, Hiroaki Kikuchi, Yukiko Nishihama, Eisei Sohara, Shinichi Uchida, Shoji F. Nakayama
Ecotoxicology and Environmental Safety  Available online: 6 November 2025
DOI:https://doi.org/10.1016/j.ecoenv.2025.119330

Highlights

  • Urinary DETP level was positively associated with blood TC and LDL-C in children.
  • A higher level of DAP mixture was associated with higher blood TC and LDL-C.
  • Enhanced mouse hepatic PPARα and PPARγ target gene expression by fenthion exposure.
  • Enhanced PPAR signaling may induce hepatic lipid uptake, oxidation, and synthesis.

Abstract

Background

While previous studies showed associations between greater organophosphate pesticide (OPP) exposure and higher blood cholesterol levels in adults, the association in children and its underlying mechanism remain unclear. We investigated the association between urinary dialkylphosphate concentrations (DAP), which reflect recent OPP exposure, and blood lipid levels in preadolescent children. We examined the effect of OPP exposure on mouse hepatic transcription factors to explore underlying mechanisms.

Methods

Using data from the National Health and Nutrition Examination Survey 1999–2002, we examined the association between DAP and blood lipid levels in 385 children aged 6–11 years, using Bayesian linear regression adjusted for potential confounders. The association between DAP and the presence of dyslipidemia was examined by Bayesian logistic regression. Using published RNA-seq data of mouse liver, we evaluated the relative abundances of target gene expressions of transcription factors relevant to hepatic lipid metabolism in mice on a fenthion-containing diet and a control diet.

Results

Over 50 % of children had detectable levels of dimethylphosphate, diethylphosphate, dimethylthiophosphate, and diethylthiophosphate. Higher diethylthiophosphate was associated with high total cholesterol level (highest vs lowest quartile group: odds ratio = 4.35, 95 % credible interval = 1.63–11.70). Target gene-set analyses revealed higher expression of PPARα and PPARγ target genes upon fenthion exposure, suggesting upregulated fatty acid oxidation and triglyceride synthesis, resembling transcriptomic changes observed in non-alcoholic fatty liver disease.

Conclusion

Higher diethylthiophosphate was associated with high blood cholesterol levels. Upregulated PPARα and PPARγ target genes may partly explain the association between OPP exposure and dyslipidemia.

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