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Environ Sci Technol. 2019 Mar 19;53(6):3287-3295. doi: 10.1021/acs.est.8b06978. Epub 2019 Mar 1.

Adipogenic Activity of Oligomeric Hexafluoropropylene Oxide (Perfluorooctanoic Acid Alternative) through Peroxisome Proliferator-Activated Receptor γ Pathway.

Li CH1,2, Ren XM1, Guo LH1,2,3.

Author information

1
State Key Laboratory of Environmental Chemistry and Eco-toxicology, Research Center for Eco-environmental Sciences , Chinese Academy of Sciences , 18 Shuangqing Road , Beijing 100085 , P. R. China.
2
College of Resources and Environment , University of Chinese Academy of Sciences , Beijing 100039 , P. R. China.
3
The Third Affiliated Hospital of Guangzhou Medical University , Guangzhou 510150 , P. R. China.

Abstract

Hexafluoropropylene oxide trimer acid (HFPO-TA) and hexafluoropropylene oxide dimer acid (HFPO-DA) have been used as perfluorooctanoic acid (PFOA) alternatives in the fluoropolymer industry for years. Their widespread environmental distribution, high bioaccumulation capability, and human exposure have caused great concern. Nevertheless, their potential toxicity and health risk remain largely unknown. In the present study, we compared potential disruption effects of HFPO-TA, HFPO-DA, and PFOA on peroxisome proliferator-activated receptor γ (PPARγ) via the investigation of receptor binding, receptor activity, and cell adipogenesis effects. The receptor binding experiment showed HFPO-TA exhibited 4.8-7.5 folds higher binding affinity with PPARγ than PFOA, whereas HFPO-DA exhibited weaker binding affinity than PFOA. They also showed agonistic activity toward PPARγ signaling pathway in HEK 293 cells in the order of HFPO-TA > PFOA > HFPO-DA. Molecular docking simulation indicated HFPO-TA formed more hydrogen bonds than PFOA, whereas HFPO-DA formed fewer hydrogen bonds than PFOA. HFPO-TA promoted adipogenic differentiation and lipid accumulation in both mouse and human preadipocytes with potency higher than PFOA. Adipogenesis in human preadipocytes is a more sensitive end point than mouse preadipocytes. Collectively, HFPO-TA exerts higher binding affinity, agonistic activity, and adipogenesis activity than PFOA. The potential health risk of HFPO-TA should be of concern.

PMID:
30785727
DOI:
10.1021/acs.est.8b06978

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