In Utero Exposure to Mercury Is Associated With Increased Susceptibility to Liver Injury and Inflammation in Childhood.
Adult
Alanine Transaminase
Child
Cohort Studies
Cytokines
Disease Susceptibility
Exposome
Female
Humans
Inflammation
Interleukin-1beta
/ genetics
Interleukin-6
/ genetics
Interleukin-8
/ genetics
Male
Maternal Exposure
Mercury
/ blood
Non-alcoholic Fatty Liver Disease
/ epidemiology
Pregnancy
Prenatal Exposure Delayed Effects
/ epidemiology
Tumor Necrosis Factor-alpha
/ genetics
Journal
Hepatology (Baltimore, Md.)
ISSN: 1527-3350
Titre abrégé: Hepatology
Pays: United States
ID NLM: 8302946
Informations de publication
Date de publication:
09 2021
09 2021
Historique:
revised:
21
01
2021
received:
26
10
2020
accepted:
23
02
2021
pubmed:
18
3
2021
medline:
13
1
2022
entrez:
17
3
2021
Statut:
ppublish
Résumé
Nonalcoholic fatty liver disease (NAFLD) is the most prevalent cause of liver disease in children. Mercury (Hg), a ubiquitous toxic metal, has been proposed as an environmental factor contributing to toxicant-associated fatty liver disease. We investigated the effect of prenatal exposure to Hg on childhood liver injury by combining epidemiological results from a multicenter mother-child cohort with complementary in vitro experiments on monocyte cells that are known to play a key role in liver immune homeostasis and NAFLD. We used data from 872 mothers and their children (median age, 8.1 years; interquartile range [IQR], 6.5-8.7) from the European Human Early-Life Exposome cohort. We measured Hg concentration in maternal blood during pregnancy (median, 2.0 μg/L; IQR, 1.1-3.6). We also assessed serum levels of alanine aminotransferase (ALT), a common screening tool for pediatric NAFLD, and plasma concentrations of inflammation-related cytokines in children. We found that prenatal Hg exposure was associated with a phenotype in children that was characterized by elevated ALT (≥22.1 U/L for females and ≥25.8 U/L for males) and increased concentrations of circulating IL-1β, IL-6, IL-8, and TNF-α. Consistently, inflammatory monocytes exposed in vitro to a physiologically relevant dose of Hg demonstrated significant up-regulation of genes encoding these four cytokines and increased concentrations of IL-8 and TNF-α in the supernatants. These findings suggest that developmental exposure to Hg can contribute to inflammation and increased NAFLD risk in early life.
Sections du résumé
BACKGROUND AND AIMS
Nonalcoholic fatty liver disease (NAFLD) is the most prevalent cause of liver disease in children. Mercury (Hg), a ubiquitous toxic metal, has been proposed as an environmental factor contributing to toxicant-associated fatty liver disease.
APPROACH AND RESULTS
We investigated the effect of prenatal exposure to Hg on childhood liver injury by combining epidemiological results from a multicenter mother-child cohort with complementary in vitro experiments on monocyte cells that are known to play a key role in liver immune homeostasis and NAFLD. We used data from 872 mothers and their children (median age, 8.1 years; interquartile range [IQR], 6.5-8.7) from the European Human Early-Life Exposome cohort. We measured Hg concentration in maternal blood during pregnancy (median, 2.0 μg/L; IQR, 1.1-3.6). We also assessed serum levels of alanine aminotransferase (ALT), a common screening tool for pediatric NAFLD, and plasma concentrations of inflammation-related cytokines in children. We found that prenatal Hg exposure was associated with a phenotype in children that was characterized by elevated ALT (≥22.1 U/L for females and ≥25.8 U/L for males) and increased concentrations of circulating IL-1β, IL-6, IL-8, and TNF-α. Consistently, inflammatory monocytes exposed in vitro to a physiologically relevant dose of Hg demonstrated significant up-regulation of genes encoding these four cytokines and increased concentrations of IL-8 and TNF-α in the supernatants.
CONCLUSIONS
These findings suggest that developmental exposure to Hg can contribute to inflammation and increased NAFLD risk in early life.
Identifiants
pubmed: 33730435
doi: 10.1002/hep.31809
pmc: PMC8446089
mid: NIHMS1708913
doi:
Substances chimiques
CXCL8 protein, human
0
Cytokines
0
IL1B protein, human
0
IL6 protein, human
0
Interleukin-1beta
0
Interleukin-6
0
Interleukin-8
0
TNF protein, human
0
Tumor Necrosis Factor-alpha
0
Alanine Transaminase
EC 2.6.1.2
Mercury
FXS1BY2PGL
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1546-1559Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK106491
Pays : United States
Organisme : NIEHS NIH HHS
ID : R21 ES029681
Pays : United States
Organisme : NIEHS NIH HHS
ID : P01 ES022845
Pays : United States
Organisme : NIEHS NIH HHS
ID : R01 ES030691
Pays : United States
Organisme : NIEHS NIH HHS
ID : R21 ES028903
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA140561
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK117004
Pays : United States
Organisme : NIEHS NIH HHS
ID : R01 ES030364
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK048522
Pays : United States
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : P01 CA196569
Pays : United States
Organisme : NIEHS NIH HHS
ID : R01 ES029944
Pays : United States
Organisme : NIEHS NIH HHS
ID : P30 ES007048
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2021 by the American Association for the Study of Liver Diseases.
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