Comparing the obesogenic effect and regulatory mechanisms of long-term exposure to per/polyfluoroalkyl substances with different terminal groups in Caenorhabditis elegans

Jia-Yu Jiang; Chun Ming How; Chi-Wei Huang; Yu-Syuan Luo; Chia-Cheng Wei

doi:10.1016/j.chemosphere.2024.143396

Comparing the obesogenic effect and regulatory mechanisms of long-term exposure to per/polyfluoroalkyl substances with different terminal groups in Caenorhabditis elegans

Chemosphere. 2024 Sep 21:143396. doi: 10.1016/j.chemosphere.2024.143396. Online ahead of print.

Authors

Jia-Yu Jiang¹, Chun Ming How¹, Chi-Wei Huang², Yu-Syuan Luo³, Chia-Cheng Wei⁴

Affiliations

¹ Institute of Food Safety and Health, College of Public Health, National Taiwan University, No. 17, Xuzhou Rd., Taipei 100, Taiwan.
² Department of Marine Environmental Engineering, National Kaohsiung University of Science and Technology, Kaohsiung 811, Taiwan.
³ Institute of Food Safety and Health, College of Public Health, National Taiwan University, No. 17, Xuzhou Rd., Taipei 100, Taiwan; Master of Public Health Program, College of Public Health, National Taiwan University, Taipei 100, Taiwan.
⁴ Institute of Food Safety and Health, College of Public Health, National Taiwan University, No. 17, Xuzhou Rd., Taipei 100, Taiwan; Department of Public Health, College of Public Health, National Taiwan University, No. 17, Xuzhou Rd., Taipei 100, Taiwan. Electronic address: ccwei@ntu.edu.tw.

PMID: 39313077
DOI: 10.1016/j.chemosphere.2024.143396

Abstract

Per/polyfluoroalkyl substances (PFASs) are ubiquitous, bioaccumulative, and recalcitrant contaminants, posing global exposure and health risks. The effects of chemical structures on toxicities and the mechanisms of their obesogenic effects were largely unclear. This study used the model organism Caenorhabditis elegans to assess the impact of long-term exposure to different PFASs (PFNA, PFOSA, PFBS, PFHxS, 6:2 FTS, 4:2 FTS, PFOA, and PFOS) on growth and lipid metabolism and discussed the obesogenic mechanisms of selected PFASs. The growth assays indicated longer carbon-fluorine (-CF) chains and total fluorine atoms increased developmental toxicity of PFASs, while at 8 -CF chain-length, PFNA (-COOH terminal), PFOS (-SO₃ terminal), and PFOSA (-SO₂NH₂ terminal) exhibited differential growth inhibition. With the toxicity ranking of PFNA>PFOS>PFOSA, all PFASs significantly induced total lipid accumulation and perturbed the lipid composition in C. elegans. All three PFASs significantly induced lipogenesis gene expression and partially suppressed lipolysis genes. The results suggested that the disruption of lipid metabolism of PFOSA depends on sbp-1, while PFNA and PFOS depend on nhr-49. In conclusion, long-term exposure to PFNA, PFOSA, and PFOS triggers obesogenic effects in organisms by distinct molecular mechanisms.

Keywords: C. elegans; Lipid metabolism; Obesity; Per/polyfluoroalkyl substances; Terminal groups.