Perfluorooctanoic acid induces liver and serum dyslipidemia in humanized PPARα mice fed an American diet.
Animals
Body Weight
/ drug effects
Caprylates
/ toxicity
Diet, Western
Dyslipidemias
/ chemically induced
Female
Fluorocarbons
/ toxicity
Gene Expression
/ drug effects
Genotype
Lipidomics
Liver
/ drug effects
Male
Mice, Transgenic
Organ Size
/ drug effects
PPAR alpha
/ genetics
Triglycerides
/ blood
United States
Lipid homeostasis
Perfluorooctanoic acid
Peroxisome proliferator activated receptor α
Triacylglyceride
Journal
Toxicology and applied pharmacology
ISSN: 1096-0333
Titre abrégé: Toxicol Appl Pharmacol
Pays: United States
ID NLM: 0416575
Informations de publication
Date de publication:
01 09 2021
01 09 2021
Historique:
received:
03
04
2021
revised:
06
07
2021
accepted:
07
07
2021
pubmed:
13
7
2021
medline:
7
8
2021
entrez:
12
7
2021
Statut:
ppublish
Résumé
Per- and polyfluoroalkyl substances (PFAS) are pervasive in the environment resulting in nearly universal detection in people. Human serum PFAS concentrations are strongly associated with increased serum low-density lipoprotein cholesterol (LDL-C), and growing evidence suggests an association with serum triacylglycerides (TG). Here, we tested the hypothesis that perfluorooctanoic acid (PFOA) dysregulates liver and serum triacylglycerides in human peroxisome proliferator activated receptor α (hPPARα)-expressing mice fed an American diet. Mice were exposed to PFOA (3.5 mg/L) in drinking water for 6 weeks resulting in a serum concentration of 48 ± 9 μg/ml. In male and female hPPARα mice, PFOA increased total liver TG and TG substituted with saturated and monounsaturated fatty acids. Lack of expression of PPARα alone also increased total liver TG, and PFOA treatment had little effect on liver TG in PPARα null mice. In hPPARα mice, PFOA neither significantly increased nor decreased serum TG; however, there was a modest increase in TG associated with very low-density cholesterol particles in both sexes. Intriguingly, in female PPARα null mice, PFOA significantly increased serum TG, with a similar trend in males. PFOA also modified fatty acid and TG homeostasis-related gene expression in liver, in a hPPARα-dependent manner, but not in adipose. The results of our study and others reveal the importance of context (serum concentration and genotype) in determining the effect of PFOA on lipid homeostasis.
Identifiants
pubmed: 34252412
pii: S0041-008X(21)00248-9
doi: 10.1016/j.taap.2021.115644
pmc: PMC8338894
mid: NIHMS1725649
pii:
doi:
Substances chimiques
Caprylates
0
Fluorocarbons
0
PPAR alpha
0
Triglycerides
0
perfluorooctanoic acid
947VD76D3L
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
115644Subventions
Organisme : NIEHS NIH HHS
ID : P42 ES007381
Pays : United States
Organisme : NIEHS NIH HHS
ID : R01 ES027813
Pays : United States
Organisme : NIH HHS
ID : S10 OD023663
Pays : United States
Informations de copyright
Copyright © 2021 Elsevier Inc. All rights reserved.
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