Chronic perfluorooctane sulfonate (PFOS) exposure induces hepatic steatosis in zebrafish

Cheng, Jiangfei; Lv, Sha; Nie, Shangfei; Liu, Jing; Tong, Shoufang; Kang, Ning; Xiao, Yanyan; Dong, Qian; Huang, Changjiang; Yang, Dongren

doi:10.1016/j.aquatox.2016.04.013

Cited by 109 publications

(49 citation statements)

References 42 publications

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“…Additionally, SCFAs, including butyrate, have been shown to act as a switch between fatty acid oxidation and lipogenesis in a PPARγ-dependent manner (den Besten et al 2015 ). Deregulated lipogenesis in the form of hepatic steatosis is commonly seen after exposure to PFOS (Cheng et al 2016 ; Lai et al 2017 ), as are perturbations to fatty acid oxidation (Wan et al 2012 ). However, laboratory results are contradictory in relation to this, with some studies indicating increased beta oxidation or gene expression of relevant enzymes (Hu et al 2005 ; Nordén et al 2012 ; Tan et al 2012 ), while others indicate beta oxidation is supressed (Adinehzadeh and Reo 1998 ; Bijland et al 2011 ; Cheng et al 2016 ).…”

Section: Discussionmentioning

confidence: 99%

Effects of perfluorooctane sulfonate on genes controlling hepatic fatty acid metabolism in livers of chicken embryos

Jacobsen

Nordén

Engwall

et al. 2018

Environ Sci Pollut Res

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Per- and polyfluoroalkyl substances (PFAS) are synthetic surfactants with a wide variety of applications; however, due to their stability, they are particularly resistant to degradation and, as such, are classed as persistent organic pollutants. Perfluorooctane sulfonate (PFOS) is one such PFAS that is still detectable in a range of different environmental settings, despite its use now being regulated in numerous countries. Elevated levels of PFOS have been detected in various avian species, and the impact of this on avian health is of interest when determining acceptable levels of PFOS in the environment. Due to its similarities to naturally occurring fatty acids, PFOS has potential to disrupt a range of biological pathways, particularly those associated with lipid metabolism, and this has been shown in various species. In this study, we have investigated how in ovo exposure to environmentally relevant levels of PFOS affects expression of genes involved in lipid metabolism of developing chicken embryos. We have found a broad suppression of transcription of genes involved in fatty acid oxidation and PPAR-mediated transcription with more significant effects apparent at lower doses of PFOS. These results highlight the need for more research investigating the biological impacts of low levels of PFAS to properly inform environmental policy governing their regulation.Electronic supplementary materialThe online version of this article (10.1007/s11356-018-2358-7) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Effects of perfluorooctane sulfonate on genes controlling hepatic fatty acid metabolism in livers of chicken embryos

Jacobsen

Nordén

Engwall

et al. 2018

Environ Sci Pollut Res

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“…A high fat, high sugar diet ( Adams and Lindor, 2007 ), genetic predisposition ( Anstee and Day, 2015 ; Liu et al, 2013 ) and alcohol abuse ( Magdaleno et al, 2017 ) are clear risk factors for FLD, but these risks alone do not account for the steep rise in FLD incidence, nor do they provide an explanation for all FLD cases. Epidemiological studies have shown that multiple environmental and anthropogenic toxicants cause liver disease in humans ( Das et al, 2010 ; Islam et al, 2011 ; Mazumder, 2005 ; Santra et al, 1999 ), and work in rodents ( Ditzel et al, 2016 ) and zebrafish ( Cheng et al, 2016 ) have demonstrated a direct, causative relationship between some environmental toxicants and FLD ( Al-Eryani et al, 2015 ; Wahlang et al, 2013 ). The combination of epidemiological and basic research on environmental toxicants and metabolic disease is rapidly advancing, yet the scope of the problem and the mechanisms of toxicity are not yet clear.…”

Section: Introductionmentioning

confidence: 99%

Inorganic arsenic causes fatty liver and interacts with ethanol to cause alcoholic liver disease in zebrafish

Bambino

Zhang

Austin

et al. 2018

Disease Models &Amp; Mechanisms

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The rapid increase in fatty liver disease (FLD) incidence is attributed largely to genetic and lifestyle factors; however, environmental toxicants are a frequently overlooked factor that can modify the effects of more common causes of FLD. Chronic exposure to inorganic arsenic (iAs) is associated with liver disease in humans and animal models, but neither the mechanism of action nor the combinatorial interaction with other disease-causing factors has been fully investigated. Here, we examined the contribution of iAs to FLD using zebrafish and tested the interaction with ethanol to cause alcoholic liver disease (ALD). We report that zebrafish exposed to iAs throughout development developed specific phenotypes beginning at 4 days post-fertilization (dpf), including the development of FLD in over 50% of larvae by 5 dpf. Comparative transcriptomic analysis of livers from larvae exposed to either iAs or ethanol revealed the oxidative stress response and the unfolded protein response (UPR) caused by endoplasmic reticulum (ER) stress as common pathways in both these models of FLD, suggesting that they target similar cellular processes. This was confirmed by our finding that arsenic is synthetically lethal with both ethanol and a well-characterized ER-stress-inducing agent (tunicamycin), suggesting that these exposures work together through UPR activation to cause iAs toxicity. Most significantly, combined exposure to sub-toxic concentrations of iAs and ethanol potentiated the expression of UPR-associated genes, cooperated to induce FLD, reduced the expression of as3mt, which encodes an arsenic-metabolizing enzyme, and significantly increased the concentration of iAs in the liver. This demonstrates that iAs exposure is sufficient to cause FLD and that low doses of iAs can potentiate the effects of ethanol to cause liver disease.This article has an associated First Person interview with the first author of the paper.

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“…Though we did not examine the histological changes of liver tissues in medaka in the present study, we expect to see similar phenotypical changes as that of zebrafish given the similarity of these two model species (small aquaria fish) and the applied PFOS doses. We thus speculate that PFOS-induced mutant frequency in λ transgenic medaka may be mediated through adverse effects on liver tissue or more specifically the lipid oxidation in the liver4243. The very recent study that reported PFOS’s mutagenic effect in vitro also observed increased lipid droplets in cells treated with PFOS and demonstrated that PFOS induced DNA double strand breaks and gene mutation was mediated by H 2 O 2 through abnormal peroxisomal fatty acid β-oxidation41.…”

Section: Discussionmentioning

confidence: 87%

Subchronic perfluorooctanesulfonate (PFOS) exposure induces elevated mutant frequency in an in vivo λ transgenic medaka mutation assay

Chen

Huang

et al. 2016

Sci Rep

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Perfluorooctanesulfonate (PFOS) has been widely detected in the environment, wildlife and humans, but few studies have ever examined its mutagenic effect in vivo. In the present study, we use a transgenic fish model, the λ transgenic medaka, to evaluate the potential mutagenicity of PFOS in vivo following a subchronic exposure of 30 days. The mutant frequency of cII target gene was 3.46 × 10−5 in liver tissue from control fish, which increased by 1.4-fold to 4.86 × 10−5 in fish exposed to 6.7 μg/L PFOS, 1.55-fold to 5.36 × 10−5 in fish exposed to 27.6 μg/L PFOS, and 2.02-fold to 6.99 × 10−5 in fish exposed to 87.6 μg/L PFOS. This dose-dependent increase of mutant frequency was also accompanied with mutational spectrum changes associated with PFOS exposure. In particular, PFOS-induced mutation was characterized by +1 frameshift mutations, which increased from 0% in control fish to 13.2% in fish exposed to 27.6 μg/L PFOS and 14.6% in fish exposed to 87.6 μg/L PFOS. Our findings provide the first evidence of PFOS’s mutagenicity in an aquatic model system. Given the fact that most conventional mutagenic assays were negative for PFOS, we propose that PFOS-induced mutation in liver tissue of λ transgenic medaka may be mediated through compromised liver function.

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Chronic perfluorooctane sulfonate (PFOS) exposure induces hepatic steatosis in zebrafish

Cited by 109 publications

References 42 publications

Effects of perfluorooctane sulfonate on genes controlling hepatic fatty acid metabolism in livers of chicken embryos

Effects of perfluorooctane sulfonate on genes controlling hepatic fatty acid metabolism in livers of chicken embryos

Inorganic arsenic causes fatty liver and interacts with ethanol to cause alcoholic liver disease in zebrafish

Subchronic perfluorooctanesulfonate (PFOS) exposure induces elevated mutant frequency in an in vivo λ transgenic medaka mutation assay

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