Perfluorohexanesulfonic Acid (PFHxS) Impairs Lipid Homeostasis in Zebrafish Larvae through Activation of PPARα

He, Ying-Jie1; Liao, Haolin2; Yang, Ge2; Qiu, Wenhui1; Xuan, Rongrong4; Zheng, Guomao5; Xu, Bentuo6; Yang, Xin5; Magnuson, Jason T.7; Schlenk, Daniel8; Zheng, Chunmiao1,3

2024-08-01

10.1021/acs.est.4c03053

ENVIRONMENTAL SCIENCE & TECHNOLOGY   影响因子和分区

0013-936X

1520-5851

Perfluorohexanesulfonic acid (PFHxS), an emerging short-chain per- and polyfluoroalkyl substance, has been frequently detected in aquatic environments. Adverse outcome pathway studies have shown that perfluorinated compounds impair lipid homeostasis through peroxisome proliferator activated receptors (PPARs). However, many of these studies were performed at high concentrations and may thus be a result of overt toxicity. To better characterize the molecular and key events of PFHxS to biota, early life-stage zebrafish (Danio rerio) were exposed to concentrations detected in the environment (0.01, 0.1, 1, and 10 mu g/L). Lipidomic and transcriptomic evaluations were integrated to predict potential molecular targets. PFHxS significantly impaired lipid homeostasis by the dysregulation of glycerophospholipids, fatty acyls, glycerolipids, sphingolipids, prenol lipids, and sterol lipids. Informatic analyses of the lipidome and transcriptome indicated alterations of the PPAR signaling pathway, with downstream changes to retinol, linoleic acid, and glycerophospholipid metabolism. To assess the role of PPARs, potential binding of PFHxS to PPARs was predicted and animals were coexposed to a PPAR antagonist (GW6471). Molecular simulation indicated PFHxS had a 27.1% better binding affinity than oleic acid, an endogenous agonist of PPAR alpha. Antagonist coexposures rescued impaired glycerophosphocholine concentrations altered by PFHxS. These data indicate PPAR alpha activation may be an important molecular initiating event for PFHxS.

PFHxS integrated omics zebrafish lipid homeostasis PPAR signaling pathway

SCI ; EI

英语

第一 ; 通讯

National Natural Science Foundation of China["42322707","42277266"] ; China Postdoctoral Science Foundation[2023M731517] ; Shenzhen Key Laboratory of Precision Measurement and Early Warning Technology for Urban Environmental Health Risks[ZDSYS20220606100604008] ; Shenzhen Science and Technology Innovation Committee[20220814233432001] ; Ningbo key research and development plan and "reveal the list" project[2023Z175] ; Guangdong Provincial Key Laboratory of Soil and Groundwater Pollution Control[2023B1212060002] ; Guangdong-Hong Kong Joint Laboratory for Soil and Groundwater Pollution Control[2023B1212120001]

Engineering ; Environmental Sciences & Ecology

Engineering, Environmental ; Environmental Sciences

WOS:001292268100001

AMER CHEMICAL SOC

ENVIRONMENT/ECOLOGY

Web of Science

1.Southern Univ Sci & Technol, Sch Environm Sci & Engn, Guangdong Prov Key Lab Soil & Groundwater Pollut C, Shenzhen 518055, Peoples R China
2.Southern Univ Sci & Technol, Sch Environm Sci & Engn, Guangdong Hong Kong Joint Lab Soil & Groundwater P, Shenzhen 518055, Guangdong, Peoples R China
3.Eastern Inst Adv Study, Eastern Inst Technol, Ningbo 315200, Peoples R China
4.Ningbo Univ, Affiliated Hosp 1, Ningbo 315020, Peoples R China
5.Southern Univ Sci & Technol, Sch Environm Sci & Engn, Shenzhen Key Lab Precis Measurement & Early Warnin, Shenzhen 518055, Peoples R China
6.Wenzhou Univ, Natl & Local Joint Engn Res Ctr Ecol Treatment Tec, Sch Life & Environm Sci, Wenzhou 325035, Peoples R China
7.US Geol Survey, Columbia Environm Res Ctr, Columbia, MO 65201 USA
8.Univ Calif Riverside, Dept Environm Sci, Riverside, CA 92521 USA

He, Ying-Jie,Liao, Haolin,Yang, Ge,et al. Perfluorohexanesulfonic Acid (PFHxS) Impairs Lipid Homeostasis in Zebrafish Larvae through Activation of PPARα[J]. ENVIRONMENTAL SCIENCE & TECHNOLOGY,2024.

He, Ying-Jie.,Liao, Haolin.,Yang, Ge.,Qiu, Wenhui.,Xuan, Rongrong.,...&Zheng, Chunmiao.(2024).Perfluorohexanesulfonic Acid (PFHxS) Impairs Lipid Homeostasis in Zebrafish Larvae through Activation of PPARα.ENVIRONMENTAL SCIENCE & TECHNOLOGY.

He, Ying-Jie,et al."Perfluorohexanesulfonic Acid (PFHxS) Impairs Lipid Homeostasis in Zebrafish Larvae through Activation of PPARα".ENVIRONMENTAL SCIENCE & TECHNOLOGY (2024).