PUBLICATION

PFHxS Exposure and the Risk of Non-Alcoholic Fatty Liver Disease

Authors

Ulhaq, Z.S., Tse, W.K.F.

ID

ZDB-PUB-240123-7

Date

2024

Source

Genes 15(1): (Journal)

Registered Authors

Ulhaq, Zulvikar Syambani

Keywords

PFAS, chronic liver disease, toxicities, transcriptomic, zebrafish

MeSH Terms

Animals
Fluorocarbons*
Humans
Insulin Resistance*/genetics
Non-alcoholic Fatty Liver Disease*/genetics
Risk Factors
Sulfonic Acids*
Zebrafish/genetics

(all 8)

PubMed

38254982 Full text @ Genes (Basel)

Abstract

Perfluorohexanesulfonic acid (PFHxS) is a highly prevalent environmental pollutant, often considered to be less toxic than other poly- and perfluoroalkyl substances (PFASs). Despite its relatively lower environmental impact compared to other PFASs, several studies have suggested that exposure to PFHxS may be associated with disruptions of liver function in humans. Nevertheless, the precise pathomechanisms underlying PFHxS-induced non-alcoholic fatty liver disease (NAFLD) remain relatively unclear. Therefore, this study applied our previously published transcriptome dataset to explore the effects of PFHxS exposure on the susceptibility to NAFLD and to identify potential mechanisms responsible for PFHxS-induced NAFLD through transcriptomic analysis conducted on zebrafish embryos. Results showed that exposure to PFHxS markedly aggravated hepatic symptoms resembling NAFLD and other metabolic syndromes (MetS) in fish. Transcriptomic analysis unveiled 17 genes consistently observed in both NAFLD and insulin resistance (IR), along with an additional 28 genes identified in both the adipocytokine signaling pathway and IR. These shared genes were also found within the NAFLD dataset, suggesting that hepatic IR may play a prominent role in the development of PFHxS-induced NAFLD. In conclusion, our study suggests that environmental exposure to PFHxS could be a potential risk factor for the development of NAFLD, challenging the earlier notion of PFHxS being safer as previously claimed.

Genes / Markers

Marker	Marker Type	Name
akt2	GENE	v-akt murine thymoma viral oncogene homolog 2
g6pc1a.1	GENE	glucose-6-phosphatase catalytic subunit 1a, tandem duplicate 1
il6	GENE	interleukin 6 (interferon, beta 2)
irs1	GENE	insulin receptor substrate 1
irs2a	GENE	insulin receptor substrate 2a
pck1	GENE	phosphoenolpyruvate carboxykinase 1 (soluble)
socs3a	GENE	suppressor of cytokine signaling 3a
srebf1	GENE	sterol regulatory element binding transcription factor 1
stat3	GENE	signal transducer and activator of transcription 3 (acute-phase response factor)
tnfa	GENE	tumor necrosis factor a (TNF superfamily, member 2)

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Figures

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Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
akt2	WT	chemical treatment by environment: perfluorohexanesulfonic acid	Day 5	whole organism	RTPCR	Figure 3
g6pc1a.1	WT	chemical treatment by environment: perfluorohexanesulfonic acid	Day 5	whole organism	RTPCR	Figure 3
il6	WT	chemical treatment by environment: perfluorohexanesulfonic acid	Day 5	whole organism	RTPCR	Figure 3
irs1	WT	chemical treatment by environment: perfluorohexanesulfonic acid	Day 5	whole organism	RTPCR	Figure 3
irs2a	WT	chemical treatment by environment: perfluorohexanesulfonic acid	Day 5	whole organism	RTPCR	Figure 3
pck1	WT	chemical treatment by environment: perfluorohexanesulfonic acid	Day 5	whole organism	RTPCR	Figure 3
socs3a	WT	chemical treatment by environment: perfluorohexanesulfonic acid	Day 5	whole organism	RTPCR	Figure 3
srebf1	WT	chemical treatment by environment: perfluorohexanesulfonic acid	Day 5	whole organism	RTPCR	Figure 3
stat3	WT	chemical treatment by environment: perfluorohexanesulfonic acid	Day 5	whole organism	RTPCR	Figure 3
tnfa	WT	chemical treatment by environment: perfluorohexanesulfonic acid	Day 5	whole organism	RTPCR	Figure 3

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT	chemical treatment by environment: perfluorohexanesulfonic acid	Day 5	autophagy increased occurrence, abnormal	Figure 1
WT	chemical treatment by environment: perfluorohexanesulfonic acid	Day 5	cardiac muscle cell hypertrophic, abnormal	Figure 1
WT	chemical treatment by environment: perfluorohexanesulfonic acid	Day 5	insulin processing decreased process quality, abnormal	Figure 1
WT	chemical treatment by environment: perfluorohexanesulfonic acid	Day 5	interleukin-17A-mediated signaling pathway increased occurrence, abnormal	Figure 1
WT	chemical treatment by environment: perfluorohexanesulfonic acid	Day 5	leptin-mediated signaling pathway increased occurrence, abnormal	Figure 1
WT	chemical treatment by environment: perfluorohexanesulfonic acid	Day 5	mitophagy increased occurrence, abnormal	Figure 1
WT	chemical treatment by environment: perfluorohexanesulfonic acid	Day 5	muscle glycogen metabolic process decreased process quality, abnormal	Figure 1
WT	chemical treatment by environment: perfluorohexanesulfonic acid	Day 5	negative regulation of amino acid biosynthetic process increased occurrence, abnormal	Figure 1
WT	chemical treatment by environment: perfluorohexanesulfonic acid	Day 5	nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway increased process quality, abnormal	Figure 1
WT	chemical treatment by environment: perfluorohexanesulfonic acid	Day 5	oxidative phosphorylation decreased process quality, abnormal	Figure 1

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Mutations / Transgenics

Human Disease / Model

Human Disease	Fish	Conditions	Evidence
metabolic dysfunction-associated steatotic liver disease	WT	chemical treatment by environment: perfluorohexanesulfonic acid	TAS

Sequence Targeting Reagents

Fish

Fish
WT

Antibodies

Orthology

Engineered Foreign Genes

Mapping

Ulhaq et al., 2024 ZDB-PUB-240123-7 PMID:38254982

PFHxS Exposure and the Risk of Non-Alcoholic Fatty Liver Disease

Ulhaq et al., 2024

ZDB-PUB-240123-7
PMID:38254982