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

ABSTRACT: 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.

SUBMITTER: Jacobsen AV

PROVIDER: S-EPMC6096545 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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

Jacobsen Annette V AV Nordén Marcus M Engwall Magnus M Scherbak Nikolai N

Environmental science and pollution research international 20180602 23

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 ...[more]

PMID: 29860686

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Project description:Perfluorooctane sulfonate (PFOS) has been widely utilized in numerous industries. Due to long environmental and biological half-lives, PFOS is a major public health concern. Although the literature suggests that PFOS may induce neurotoxicity, neurotoxic mechanisms, and neuropathology are poorly understood. Thus, the primary goal of this study was to determine if PFOS is selectively neurotoxic and potentially relevant to specific neurological diseases. Nematodes (Caenorhabditis elegans) were exposed to PFOS or related per- and polyfluoroalkyl substances (PFAS) for 72 h and tested for evidence of neuropathology through examination of cholinergic, dopaminergic, gamma-amino butyric acid (GABA)ergic, and serotoninergic neuronal morphologies. Dopaminergic and cholinergic functional analyses were assessed through 1-nonanol and Aldicarb assay. Mechanistic studies assessed total reactive oxygen species, superoxide ions, and mitochondrial content. Finally, therapeutic approaches were utilized to further examine pathogenic mechanisms. Dopaminergic neuropathology occurred at lower exposure levels (25 ppm, approximately 50 µM) than required to produce neuropathology in GABAergic, serotonergic, and cholinergic neurons (100 ppm, approximately 200 µM). Further, PFOS exposure led to dopamine-dependent functional deficits, without altering acetylcholine-dependent paralysis. Mitochondrial content was affected by PFOS at far lower exposure level than required to induce pathology (≥1 ppm, approximately 2 µM). Perfluorooctane sulfonate exposure also enhanced oxidative stress. Further, mutation in mitochondrial superoxide dismutase rendered animals more vulnerable. Neuroprotective approaches such as antioxidants, PFAS-protein dissociation, and targeted (mitochondrial) radical and electron scavenging were neuroprotective, suggesting specific mechanisms of action. In general, other tested PFAS were less neurotoxic. The primary impact is to prompt research into potential adverse outcomes related to PFAS-induced dopaminergic neurotoxicity in humans.

Project description:BackgroundHuman and animal studies have raised concerns that supplemental selenium can increase the risk of metabolic disorders, but underlying mechanisms are unclear.ObjectiveWe used an integrated transcriptome and metabolome analysis of liver to test for functional pathway and network responses to supplemental selenium in mice.MethodsMale mice (8-wk-old, C57BL/6J) fed a standard diet (0.41 ppm Se) were given selenium (Na2SeO4, 20 μmol/L) or vehicle (drinking water) for 16 wk. Livers were analyzed for selenium concentration, activity of selenoproteins, reduced glutathione (GSH) redox state, gene expression, and high-resolution metabolomics. Transcriptomic and nontargeted metabolomic data were analyzed with biostatistics, bioinformatics, pathway enrichment analysis, and combined transcriptome-metabolome-wide association study (TMWAS).ResultsMice supplemented with selenium had greater body mass gain from baseline to 16 wk (55% ± 5%) compared with controls (40% ± 3%) (P < 0.05); however, no difference was observed in liver selenium content, selenoenzyme transcripts, or enzyme activity. Selenium was higher in the heart, kidney, and urine of mice supplemented with selenium. Gene enrichment analysis showed that supplemental selenium altered pathways of lipid and energy metabolism. Integrated transcriptome and metabolome network analysis showed 2 major gene-metabolite clusters, 1 centered on the transcript for the bidirectional glucose transporter 2 (Glut2) and the other centered on the transcripts for carnitine-palmitoyl transferase 2 (Cpt2) and acetyl-CoA acyltransferase (Acaa1). Pathway analysis showed that highly associated metabolites (P < 0.05) were enriched in fatty acid metabolism and bile acid biosynthesis, including acylcarnitines, triglycerides and glycerophospholipids, long-chain acyl-coenzyme As, phosphatidylcholines, and sterols. TMWAS of body weight gain confirmed changes in the same pathways.ConclusionsSupplemental selenium in mice alters hepatic fatty acid and energy metabolism and causes increases in body mass. A lack of effect on hepatic selenium content suggests that signaling involves an extrahepatic mechanism.

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

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

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