Mitochondrial dysfunction in metabolic disorders induced by per- and polyfluoroalkyl substance mixtures in zebrafish larvae

Several per- and polyfluoroalkyl substances (PFAS) have been linked to metabolic disorders in organisms. However, few studies have considered their combined effects, which would be more representative of PFAS occurring in the environment. In this study, zebrafish embryos were exposed to a mixture of...

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Main Authors: Yingxin Liu, Shuai Liu, Jing Huang, Yu Liu, Qiyu Wang, Jinyuan Chen, Liwei Sun, Wenqing Tu
Format: Article
Language:English
Published: Elsevier 2023-06-01
Series:Environment International
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0160412023002507
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author Yingxin Liu
Shuai Liu
Jing Huang
Yu Liu
Qiyu Wang
Jinyuan Chen
Liwei Sun
Wenqing Tu
author_facet Yingxin Liu
Shuai Liu
Jing Huang
Yu Liu
Qiyu Wang
Jinyuan Chen
Liwei Sun
Wenqing Tu
author_sort Yingxin Liu
collection DOAJ
description Several per- and polyfluoroalkyl substances (PFAS) have been linked to metabolic disorders in organisms. However, few studies have considered their combined effects, which would be more representative of PFAS occurring in the environment. In this study, zebrafish embryos were exposed to a mixture of 18 PFAS at three environmentally relevant concentrations for 5 days to assess their bioconcentration and metabolic consequences. The burdens of ∑PFAS in zebrafish larvae were 0.12, 1.58, and 9.63 mg/kg in the 0.5, 5, and 50 μg/L treatment groups, respectively. Exposure to the PFAS mixture accelerated hatching and larval heart rates, increased energy expenditure, and reduced ATP levels and glucose contents due to decreased feed intake and glucose uptake. Metabolomic analysis revealed that exposure to the PFAS mixture enhanced glycolysis but inhibited phospholipid synthesis, and significantly increased the expression of lipid metabolism related genes (srebf1, acox, and pparα), which indicated enhanced β-oxidation. The significant changes in mitochondrial membrane potential, mitochondrial content, and the transcription of genes involved in the mitochondrial respiratory chain (mfn2, ndufs1, atp5fa1, and mt-nd1) and mitochondrial DNA replication and transcription (18rs-rrn, and polg1) suggested that exposure to the PFAS mixture could cause mitochondrial dysfunction and further disrupt glucose and lipid metabolic pathways, ultimately causing metabolic disorders in zebrafish larvae. These findings demonstrate the importance of assessing the metabolic effects of PFAS mixtures on early development in wildlife and humans.
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spelling doaj.art-8aeb687e2b4a4945829aa35a057624b72023-06-04T04:23:06ZengElsevierEnvironment International0160-41202023-06-01176107977Mitochondrial dysfunction in metabolic disorders induced by per- and polyfluoroalkyl substance mixtures in zebrafish larvaeYingxin Liu0Shuai Liu1Jing Huang2Yu Liu3Qiyu Wang4Jinyuan Chen5Liwei Sun6Wenqing Tu7College of Environment, Zhejiang University of Technology, Hangzhou 310014, China; School of New Energy Science and Engineering, Xinyu University, Xinyu 338004, China; Research Institute of Poyang Lake, Jiangxi Academy of Sciences, Nanchang 330012, ChinaResearch Institute of Poyang Lake, Jiangxi Academy of Sciences, Nanchang 330012, ChinaKey Laboratory of Poyang Lake Basin Agricultural Resource and Ecology of Jiangxi Province, College of Land Resource and Environment, Jiangxi Agricultural University, Nanchang 330045, ChinaResearch Institute of Poyang Lake, Jiangxi Academy of Sciences, Nanchang 330012, ChinaResearch Institute of Poyang Lake, Jiangxi Academy of Sciences, Nanchang 330012, ChinaCollege of Environment, Zhejiang University of Technology, Hangzhou 310014, China; Corresponding authors.College of Environment, Zhejiang University of Technology, Hangzhou 310014, ChinaKey Laboratory of Poyang Lake Basin Agricultural Resource and Ecology of Jiangxi Province, College of Land Resource and Environment, Jiangxi Agricultural University, Nanchang 330045, China; Corresponding authors.Several per- and polyfluoroalkyl substances (PFAS) have been linked to metabolic disorders in organisms. However, few studies have considered their combined effects, which would be more representative of PFAS occurring in the environment. In this study, zebrafish embryos were exposed to a mixture of 18 PFAS at three environmentally relevant concentrations for 5 days to assess their bioconcentration and metabolic consequences. The burdens of ∑PFAS in zebrafish larvae were 0.12, 1.58, and 9.63 mg/kg in the 0.5, 5, and 50 μg/L treatment groups, respectively. Exposure to the PFAS mixture accelerated hatching and larval heart rates, increased energy expenditure, and reduced ATP levels and glucose contents due to decreased feed intake and glucose uptake. Metabolomic analysis revealed that exposure to the PFAS mixture enhanced glycolysis but inhibited phospholipid synthesis, and significantly increased the expression of lipid metabolism related genes (srebf1, acox, and pparα), which indicated enhanced β-oxidation. The significant changes in mitochondrial membrane potential, mitochondrial content, and the transcription of genes involved in the mitochondrial respiratory chain (mfn2, ndufs1, atp5fa1, and mt-nd1) and mitochondrial DNA replication and transcription (18rs-rrn, and polg1) suggested that exposure to the PFAS mixture could cause mitochondrial dysfunction and further disrupt glucose and lipid metabolic pathways, ultimately causing metabolic disorders in zebrafish larvae. These findings demonstrate the importance of assessing the metabolic effects of PFAS mixtures on early development in wildlife and humans.http://www.sciencedirect.com/science/article/pii/S0160412023002507PFAS mixturesMetabolic disordersMitochondrial functionZebrafish
spellingShingle Yingxin Liu
Shuai Liu
Jing Huang
Yu Liu
Qiyu Wang
Jinyuan Chen
Liwei Sun
Wenqing Tu
Mitochondrial dysfunction in metabolic disorders induced by per- and polyfluoroalkyl substance mixtures in zebrafish larvae
Environment International
PFAS mixtures
Metabolic disorders
Mitochondrial function
Zebrafish
title Mitochondrial dysfunction in metabolic disorders induced by per- and polyfluoroalkyl substance mixtures in zebrafish larvae
title_full Mitochondrial dysfunction in metabolic disorders induced by per- and polyfluoroalkyl substance mixtures in zebrafish larvae
title_fullStr Mitochondrial dysfunction in metabolic disorders induced by per- and polyfluoroalkyl substance mixtures in zebrafish larvae
title_full_unstemmed Mitochondrial dysfunction in metabolic disorders induced by per- and polyfluoroalkyl substance mixtures in zebrafish larvae
title_short Mitochondrial dysfunction in metabolic disorders induced by per- and polyfluoroalkyl substance mixtures in zebrafish larvae
title_sort mitochondrial dysfunction in metabolic disorders induced by per and polyfluoroalkyl substance mixtures in zebrafish larvae
topic PFAS mixtures
Metabolic disorders
Mitochondrial function
Zebrafish
url http://www.sciencedirect.com/science/article/pii/S0160412023002507
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