Exogenous and Endogenous Serine Deficiency Exacerbates Hepatic Lipid Accumulation

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.

Section: Discussionsupporting

confidence: 89%

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

Beccacece¹,

Costa²,

et al. 2023

Preprint

“…Our analysis predicted three aminoacids amongst the top 10 metabolites downregulated by PFAS: Serine, Lysine and Glutamate (Figure 7). The downregulation of Serine agrees with current literature displaying that Serine deficiency is associated with increase in lipid accumulation in liver [112], a mechanism that mimics the impact of exposure to PFAS [12,47,79,108]. Lysine is an essential metabolite for a healthy pregnancy [113] and its deficiency is known to be detrimental to embryonal development [114], while Glutamate is essential for embryonal neurogenesis [115].…”

Section: Discussionsupporting

confidence: 89%

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.

“…Moreover, Leucine levels were found to be increased in children with high prenatal exposure to PFAS molecules and these high levels are associated with a risk of liver injury [86]. Another aminoacid shown to be significantly downregulated by PFAS is Serine (Figure 7), which is compatible with current literature, since deficiency in Serine has been causally linked with a reduction in lipid accumulation in the liver, a mechanism that mimics the impact of exposure to PFAS [111]. Another PFOS-induced metabolite is reduced Glutathione (Figure 7), a thiol compound that protects cells from oxidative stress and maintains redox homeostasis.…”

Section: Discussionsupporting

confidence: 84%

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 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.