Associations among perfluorooctanesulfonic/perfluorooctanoic acid levels, nuclear receptor gene polymorphisms, and lipid levels in pregnant women in the Hokkaido study

Kobayashi, Sumitaka; Sata, Fumihiro; Goudarzi, Houman; Araki, Atsuko; Miyashita, Chihiro; Sasaki, Seiko; Okada, Emiko; Iwasaki, Yusuke; Nakajima, Tamie; Kishi, Reiko

doi:10.1038/s41598-021-89285-2

Cited by 13 publications

(4 citation statements)

References 80 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…32 There are two gene-environment interaction studies regarding PFAS exposure. One demonstrates that polymorphisms in PPARGC1A and PPARD genes modify PFAS' associations with triglycerides and fatty acids in pregnant Japanese women, 33 while another found that polymorphisms in ABCA1, FTO, PPARG and SLC12A3 modify associations with insulin sensitivity. 34 Lastly, one study shows associations between gene expression involved in cholesterol metabolism (i.e.…”

Section: Molecular Mechanismsmentioning

confidence: 99%

Per‐ and polyfluoroalkyl substances and cardiometabolic diseases: A review

Schillemans,

Donat‐Vargas,

Åkesson

2023

Basic Clin Pharma Tox

View full text Add to dashboard Cite

Per‐ and polyfluoroalkyl substances (PFAS) are a group of persistent and widespread environmental pollutants that represent a high concern for human health. They have been shown to be associated with several important physiological processes such as lipid metabolism and the immune system. Consequently, PFAS are suspected to play a role in cardiometabolic disease development. However, the evidence regarding associations between PFAS and overt cardiovascular disease and type 2 diabetes remains limited and inconsistent. To address this, we conducted a review of the epidemiological evidence. A deeper understanding of potential underlying molecular mechanisms may help to explain inconsistencies in epidemiological findings. Thus, to gain more mechanistic insight, we also summarized evidence from omics and laboratory studies into an adverse outcome pathway framework. Our observations indicate the potential for associations of PFAS with multiple molecular pathways that could have opposite associations with disease risk, which could be further modified by mixture composition, lifestyle factors or genetic polymorphisms. This identifies the need for exposome studies considering mixture effects, the use of multi‐omics data to gain insight in relevant pathways and the integration of epidemiological and laboratory studies to enhance mechanistic understanding and causal inference. Improved comprehension is essential for environmental health risk assessments.

show abstract

Section: Molecular Mechanismsmentioning

confidence: 99%

Per‐ and polyfluoroalkyl substances and cardiometabolic diseases: A review

Schillemans,

Donat‐Vargas,

Åkesson

2023

Basic Clin Pharma Tox

View full text Add to dashboard Cite

show abstract

“…The interactions of PFASs with biological molecules such as proteins and membranes have been the subject of extensive research. − A recent review elucidated these interactions, shedding light on the molecular mechanisms through which PFASs can affect cellular processes . Previous studies have also highlighted the potential risks PFASs pose to human health, linking them to developmental toxicity, , immunotoxicity, , hepatotoxicity, and tumorigenesis .…”

Section: Introductionmentioning

confidence: 99%

Prediction of the Interactions of a Large Number of Per- and Poly-Fluoroalkyl Substances with Ten Nuclear Receptors

Azhagiya Singam,

Durkin,

La Merrill

et al. 2024

Environ. Sci. Technol.

View full text Add to dashboard Cite

Per-and poly-fluoroalkyl substances (PFASs) are persistent, toxic chemicals that pose significant hazards to human health and the environment. Screening large numbers of chemicals for their ability to act as endocrine disruptors by modulating the activity of nuclear receptors (NRs) is challenging because of the time and cost of in vitro and in vivo experiments. For this reason, we need computational approaches to screen these chemicals and quickly prioritize them for further testing. Here, we utilized molecular modeling and machine-learning predictions to identify potential interactions between 4545 PFASs with ten different NRs. The results show that some PFASs can bind strongly to several receptors. Further, PFASs that bind to different receptors can have very different structures spread throughout the chemical space. Biological validation of these in silico findings should be a high priority.

show abstract

“…Although the impact of PFAS on metabolic processes has been described in humans [23][24][25] and other animal models, such as water fleas (Daphnia) and zebrafish (Danio rerio) [26][27][28][29], this biological understanding remains limited for turtles (and other reptiles and amphibians). To date, a growing body of work by Beale and co-authors [22,30] describes alterations in the metabolic profiling of serum and oviducal eggs from turtles exposed to elevated PFAS, suggesting an inflammation response, metabolic preservation, and re-routing of central carbon metabolites.…”

Section: Introductionmentioning

confidence: 99%

Host–Gut Microbiome Metabolic Interactions in PFAS-Impacted Freshwater Turtles (Emydura macquarii macquarii)

et al. 2022

View full text Add to dashboard Cite

Per-and polyfluoroalkyl substances (PFAS) are a growing concern for humans, wildlife, and more broadly, ecosystem health. Previously, we characterised the microbial and biochemical impact of elevated PFAS on the gut microbiome of freshwater turtles (Emydura macquarii macquarii) within a contaminated catchment in Queensland, Australia. However, the understanding of PFAS impacts on this species and other aquatic organisms is still very limited, especially at the host–gut microbiome molecular interaction level. To this end, the present study aimed to apply these leading-edge omics technologies within an integrated framework that provides biological insight into the host turtle–turtle gut microbiome interactions of PFAS-impacted wild-caught freshwater turtles. For this purpose, faecal samples from PFAS-impacted turtles (n = 5) and suitable PFAS-free reference turtles (n = 5) were collected and analysed. Data from 16S rRNA gene amplicon sequencing and metabolomic profiling of the turtle faeces were integrated using MetOrigin to assign host, microbiome, and co-metabolism activities. Significant variation in microbial composition was observed between the two turtle groups. The PFAS-impacted turtles showed a higher relative abundance of Firmicutes and a lower relative abundance of Bacteroidota than the reference turtles. The faecal metabolome showed several metabolites and pathways significantly affected by PFAS exposure. Turtles exposed to PFAS displayed altered amino acid and butanoate metabolisms, as well as altered purine and pyrimidine metabolism. It is predicted from this study that PFAS-impacted both the metabolism of the host turtle and its gut microbiota which in turn has the potential to influence the host’s physiology and health.

show abstract

Associations among perfluorooctanesulfonic/perfluorooctanoic acid levels, nuclear receptor gene polymorphisms, and lipid levels in pregnant women in the Hokkaido study

Cited by 13 publications

References 80 publications

Per‐ and polyfluoroalkyl substances and cardiometabolic diseases: A review

Per‐ and polyfluoroalkyl substances and cardiometabolic diseases: A review

Prediction of the Interactions of a Large Number of Per- and Poly-Fluoroalkyl Substances with Ten Nuclear Receptors

Host–Gut Microbiome Metabolic Interactions in PFAS-Impacted Freshwater Turtles (Emydura macquarii macquarii)

Contact Info

Product

Resources

About