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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Elsevier
2023-06-01
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Series: | Environment International |
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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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series | Environment International |
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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