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

Jacobsen, Annette V.; Nordén, Marcus; Engwall, Magnus; Scherbak, Nikolai

doi:10.1007/s11356-018-2358-7

Cited by 37 publications

(24 citation statements)

References 43 publications

(59 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In a recent study, Jacobsen et al . (2018) found that exposure of chicken embryos to PFOS at 0.1 and 1 µg/g egg from E4 to E19 caused broad downregulation of genes involved in lipid metabolism in the liver 53 . Two of the most consistently downregulated genes in their study were ACAA2 and FABP5 .…”

Section: Discussionmentioning

confidence: 99%

Developmental exposure to a mixture of perfluoroalkyl acids (PFAAs) affects the thyroid hormone system and the bursa of Fabricius in the chicken

Mattsson

Sjöberg

Kärrman

et al. 2019

Sci Rep

View full text Add to dashboard Cite

Perfluoroalkyl acids (PFAAs) are ubiquitous environmental contaminants and eggs and nestlings of raptors and fish-eating birds often contain high levels of PFAAs. We studied developmental effects of a mixture of ten PFAAs by exposing chicken embryos to 0.5 or 3 μg/g egg of each compound in the mixture. Histological changes of the thyroid gland were noted at both doses and increased expression of mRNA coding for type III deiodinase was found at 0.5 μg/g egg. Serum concentrations of the free fraction of thyroid hormones (T3 and T4) were reduced by the PFAA mixture at 3 µg/g egg, which is in line with a decreased synthesis and increased turnover of thyroid hormones as indicated by our histological findings and the decreased mRNA expression of type III deiodinase. The relative weight of the bursa of Fabricius increased at a dose of 3 μg/g egg in females. The bursa is the site of B-cell development in birds and is crucial for the avian adaptive immune system. Analysis of plasma and liver concentrations of the mixture components showed differences depending on chain length and functional group. Our results highlight the vulnerability of the thyroid hormone and immune systems to PFAAs.

show abstract

Section: Discussionmentioning

confidence: 99%

Developmental exposure to a mixture of perfluoroalkyl acids (PFAAs) affects the thyroid hormone system and the bursa of Fabricius in the chicken

Mattsson

Sjöberg

Kärrman

et al. 2019

Sci Rep

View full text Add to dashboard Cite

show abstract

“…PPAR mediated dysregulation of these metabolic processes contributes to the pathogenesis of metabolic diseases such as obesity, metabolic syndrome, diabetes, and non-alcoholic fatty liver disease (NAFLD) (Gross et al 2017;Pawlak et al 2015;Semple et al 2006). The ability of some xenobiotics, such as phthalates (Casals-Casas et al 2008;Ito and Nakajima 2008;Li, Y. et al 2017), per-and polyfluoroalkyl substances (PFAS) (Behr et al 2019;Jacobsen et al 2018;Zhao et al 2017) and some others (Casals-Casas et al 2008;Peraza et al 2006) to interfere with PPAR signaling is long-recognized (Xi et al 2020). However, to our knowledge, promiscuous sensitivity of the PPAR regulatory cascade to a broad range of chemical agents has not shown before.…”

Section: Lipid Metabolism and Ppar Signalingmentioning

confidence: 99%

Unbiased approach for the identification of molecular mechanisms sensitive to chemical exposures

et al. 2021

View full text Add to dashboard Cite

Background: Targeted methods that dominated toxicological research until recently did not allow for screening of all molecular changes involved in toxic response. Therefore, it is difficult to infer if all major mechanisms of toxicity have already been discovered, or if some of them are still overlooked.Objectives: To identify molecular mechanisms sensitive to chemical exposures in an unbiased manner.Methods: We used data on 641,516 unique chemical-gene interactions from the Comparative Toxicogenomic Database. Only data from high-throughput gene expression experiments with human, rat or mouse cells/tissues were extracted. The total number of chemical-gene interactions was calculated for every gene, and used as a measure of gene sensitivity to chemical exposures. These values were further used in enrichment analyses to identify molecular mechanisms sensitive to chemical exposures.Results: Remarkably, use of different input subsets with non-overlapping lists of chemical compounds identified largely the same genes and molecular pathways as most sensitive to chemical exposures, indicative of an unbiased nature of our analysis. One of the most important findings of this study is that almost every known molecular mechanism may be affected by chemical exposures. Predictably, xenobiotic metabolism pathways and mechanisms of cellular response to stress and damage were among the most sensitive. Additionally, our analysis identified a range of highly sensitive molecular pathways, which are not widely recognized by modern toxicology as major targets of toxicants, including lipid metabolism pathways, longevity regulation cascade and cytokine mediated signaling.Discussion: Molecular mechanisms identified as the most sensitive to chemical exposures are relevant for significant public health problems, such as aging, cancer, metabolic and autoimmune disease. Thus, public health system will likely benefit from future research focus on these sensitive molecular mechanisms. Additionally, approach used in this study may guide identification of priority adverse outcome pathways (AOP) for in-vitro and in-silico toxicity testing methods.

show abstract

“… 39 In chickens, exposure to PFOS resulted in a reduction of transcription of genes involved in fatty acid oxidation and PPAR-mediated transcription. 40 In utero exposure in mice increased liver content of triglyceride, total cholesterol, and LDL. In parallel, transcription of cytochrome P4A14 for fatty acid oxidation, CD36 for hepatic fatty acid uptake, and apolipoprotein B100 and fibroblast growth factor 21 for hepatic export of lipids were altered.…”

Section: Pfas and Liver Fatmentioning

confidence: 99%

Are Persistent Organic Pollutants Linked to Lipid Abnormalities, Atherosclerosis and Cardiovascular Disease? A Review

Lind

2020

J Lipid Atheroscler

View full text Add to dashboard Cite

The term persistent organic pollutants (POPs) denotes chemicals with known or suspected adverse health effects in animals or humans and with chemical properties that make them accumulate in the environment, including animals or humans. Lipid-soluble POPs, like dioxins, polychlorinated biphenyls (PCBs) and organochlorine pesticides are transported by lipoproteins and accumulate in adipose tissue. High levels of these compounds in the circulation have been associated with elevated cholesterol and triglycerides in crosssectional studies and with an increase in mainly low-density lipoprotein cholesterol in a longitudinal study. Also, non-lipid-soluble POPs, such as perfluoroalkyl substances (PFASs) compounds have been associated with increased total cholesterol levels. Carotid artery atherosclerosis has been related to elevated levels of mainly highly chlorinated PCBs and to highly fluorinated PFASs, but in this case only in women. Both cross-sectional and prospective studies have shown dioxins, PCBs, as well as PFASs to be linked to cardiovascular disease (CVD) and mortality. In conclusion, as highlighted in this review, several lines of evidence support the view that POPs of different chemical classes could be linked to lipid abnormalities, carotid atherosclerosis and overt CVD like myocardial infarction and stroke.

show abstract

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

Cited by 37 publications

References 43 publications

Developmental exposure to a mixture of perfluoroalkyl acids (PFAAs) affects the thyroid hormone system and the bursa of Fabricius in the chicken

Developmental exposure to a mixture of perfluoroalkyl acids (PFAAs) affects the thyroid hormone system and the bursa of Fabricius in the chicken

Unbiased approach for the identification of molecular mechanisms sensitive to chemical exposures

Are Persistent Organic Pollutants Linked to Lipid Abnormalities, Atherosclerosis and Cardiovascular Disease? A Review

Contact Info

Product

Resources

About