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Citation
Tags
HERO ID
5024251
Reference Type
Journal Article
Title
Adipogenic Activity of Oligomeric Hexafluoropropylene Oxide (Perfluorooctanoic Acid Alternative) through Peroxisome Proliferator-Activated Receptor γ Pathway
Author(s)
Li, CH; Ren, XM; Guo, LH
Year
2019
Is Peer Reviewed?
1
Journal
Environmental Science & Technology
ISSN:
0013-936X
EISSN:
1520-5851
Publisher
AMER CHEMICAL SOC
Location
WASHINGTON
Volume
53
Issue
6
Page Numbers
3287-3295
Language
English
PMID
30785727
DOI
10.1021/acs.est.8b06978
Web of Science Id
WOS:000462098000038
URL
https://pubs.acs.org/doi/10.1021/acs.est.8b06978
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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.
Tags
PFAS
•
Additional PFAS (formerly XAgency)
Literature Search November 2019
Other Sources
TEDX
Screened Studies
Excluded
Exclude (TIAB)
•
Expanded PFAS SEM (formerly PFAS 430)
Litsearch: September 2019
PubMed
Other Sources
PFAS TOX Database
Screened Studies
Excluded
Exclude (TIAB)
Not prioritized for screening
Potassium perfluorooctanoate
Sodium perfluorooctanoate
•
GenX Chemicals (CASRN 13252-13-6 and CASRN 62037-80-3)
LitSearch GenX Ammonium Salt: Feb 2018 - Feb 2019
PubMed
•
PFAS 150
Literature Search Update December 2020
PubMed
WOS
Literature Search August 2019
PubMed
Web of Science
Other sources
PFAS TOX Database
Screened Studies
Excluded
Exclude (TIAB)
Ammonium perfluoro-2-methyl-3-oxahexanoate
Ammonium perfluorooctanoate
Perfluoro(2-methyl-3-oxahexanoyl) fluoride
Perfluoro-2,5-dimethyl-3,6-dioxanonanoic acid
Perfluoro-2-methyl-3-oxahexanoic acid
Perfluorooctanoic acid
•
PFOA (335-67-1) and PFOS (1763-23-1)
Literature Search Update (2013-2019)
PubMed
WOS
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