Perfluoroalkyl substance (PFAS) exposure and risk of nonalcoholic fatty liver disease in the elderly: results from NHANES 2003–2014

et al. 2023

Preprint

In the recent decades, per- and polyfluoroalkyl substances (PFAS) have garnered widespread public attention due to their persistence in the environment and detrimental effects on the health of living organisms, spurring the generation of several transcriptome-centered investigations to understand the biological basis of their mechanism. In this study, we analyzed 2144 publicly available datasets from 7 distinct species to examine the molecular responses to PFAS exposure and determine if there are conserved responses. Our comparative transcriptional analysis revealed that exposure to PFAS is conserved across different tissues, molecules and species. We identified and reported several genes exhibiting consistent and evolutionarily conserved transcriptional re-sponse to PFAS, such as ESR1, HADHA and ID1, as well as several pathways including lipid me-tabolism, immune response and hormone pathways. This study provides the first evidence that distinct PFAS molecules induce comparable transcriptional changes and affect the same metabolic processes across inter-species borders. Our findings have significant implications for under-standing the impact of PFAS exposure on living organisms and the environment. We believe that this study offers a novel perspective on the molecular responses to PFAS exposure and provides a foundation for future research into developing strategies for mitigating the detrimental effects of these substances.

Section: Correlation Analysissupporting

confidence: 88%

Section: Discussionsupporting

confidence: 64%

Section: Pathway Enrichment Analysismentioning

confidence: 99%

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Cross-species Transcriptomics Analysis Highlights Conserved Molecular Responses to Per- and Polyfluoroalkyl Substances (PFAS)

Beccacece¹,

Costa²,

et al. 2023

Preprint

“…Remarkably, CYP4A11 up-regulation has been associated with non-alcoholic fatty liver disease (NAFLD), since it increases the intracellular production of reactive oxygen species (ROS) and pro-inflammatory cytokines [72]. Our result is in line with data showing that exposure to PFOA is positively related to NAFLD development [73]. The other upregulated genes (Figure 2B) are mainly implicated in lipid metabolism, mitochondrial function, and stress response, while downregulated genes participate in immune response and inflammation, thrombosis, and cellular adhesion.…”

Section: Correlation Analysissupporting

confidence: 88%

Cross-species Transcriptomics Analysis Highlights Conserved Molecular Responses to Per- and Polyfluoroalkyl Substances (PFAS)

Beccacece¹,

Costa²,

et al. 2023

Preprint

In the recent decades, per- and polyfluoroalkyl substances (PFAS) have garnered widespread public attention due to their persistence in the environment and detrimental effects on the health of living organisms, spurring the generation of several transcriptome-centered investigations to understand the biological basis of their mechanism. In this study, we collected 2144 publicly available samples from 7 distinct animal species to examine the molecular responses to PFAS exposure and to determine if there are conserved responses. Our comparative transcriptional analysis revealed that exposure to PFAS is conserved across different tissues, molecules and species. We identified and reported several genes exhibiting consistent and evolutionarily conserved transcriptional response to PFAS, such as ESR1, HADHA and ID1, as well as several pathways including lipid metabolism, immune response and hormone pathways. This study provides the first evidence that distinct PFAS molecules induce comparable transcriptional changes and affect the same metabolic processes across inter-species borders. Our findings have significant implications for understanding the impact of PFAS exposure on living organisms and the environment. We believe that this study offers a novel perspective on the molecular responses to PFAS exposure and provides a foundation for future research into developing strategies for mitigating the detrimental effects of these substances in the ecosystem.

“…The relationship between dyslipidemia and PFAS has also been found in human children and adolescents [80], where the exposure to these chemicals increases the risk of developing NASH and NAFLD [81] as well as impairing glucose metabolism [106]. Notably, we found that CYP4A11, previously associated with NAFLD [72,73], is highly up-regulated in both humans and mice, possibly indicating a causative role in NASH development due to PFAS exposure. The impact of PFAS on children is a crucial issue, and it seems that these chemicals can even be transferred through breastfeeding [17,18], which is of great concern.…”

Section: Discussionsupporting

confidence: 64%

Cross-species Transcriptomics Analysis Highlights Conserved Molecular Responses to Per- and Polyfluoroalkyl Substances (PFAS)

Beccacece¹,

Costa²,

et al. 2023

Preprint

In the recent decades, per- and polyfluoroalkyl substances (PFAS) have garnered widespread public attention due to their persistence in the environment and detrimental effects on the health of living organisms, spurring the generation of several transcriptome-centered investigations to understand the biological basis of their mechanism. In this study, we collected 2144 publicly available samples from 7 distinct species to examine the molecular responses to PFAS exposure and to determine if there are conserved responses. Our comparative transcriptional analysis revealed that exposure to PFAS is conserved across different tissues, molecules and species. We identified and reported several genes exhibiting consistent and evolutionarily conserved transcriptional response to PFAS, such as ESR1, HADHA and ID1, as well as several pathways including lipid metabolism, immune response and hormone pathways. This study provides the first evidence that distinct PFAS molecules induce comparable transcriptional changes and affect the same metabolic processes across inter-species borders. Our findings have significant implications for understanding the impact of PFAS exposure on living organisms and the environment. We believe that this study offers a novel perspective on the molecular responses to PFAS exposure and provides a foundation for future research into developing strategies for mitigating the detrimental effects of these substances.