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Citation
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HERO ID
758808
Reference Type
Journal Article
Title
Microgram-order ammonium perfluorooctanoate may activate mouse peroxisome proliferator-activated receptor alpha, but not human PPARalpha
Author(s)
Nakamura, T; Ito, Y; Yanagiba, Y; Ramdhan, DH; Kono, Y; Naito, H; Hayashi, Y; Li, Y; Aoyama, T; Gonzalez, FJ; Nakajima, T
Year
2009
Is Peer Reviewed?
1
Journal
Toxicology
ISSN:
0300-483X
EISSN:
1879-3185
Volume
265
Issue
1-2
Page Numbers
27-33
Language
English
PMID
19751795
DOI
10.1016/j.tox.2009.09.004
Web of Science Id
WOS:000271713500004
Abstract
Perfluorooctanoic acid (PFOA) is a ligand for peroxisome proliferator-activated receptor (PPAR) alpha, which exhibits marked species differences in expression and function, especially between rodents and humans. We investigated the functional difference in PFOA response between mice and humans, using a humanized PPARalpha transgenic mouse line. Three genotyped mice, 129/Sv wild-type (mPPARalpha), Pparalpha-null mice and humanized PPARalpha (hPPARalpha) mice (8-week-old males) were divided into three groups: the first was treated with water daily for 2 weeks by gavage (control group), and the remaining two groups were treated with 0.1 and 0.3mg/kg ammonium perflurooctanate (APFO), respectively, for 2 weeks by gavage. The APFO dosages used did not influence the plasma triglyceride or total cholesterol levels in any mouse line, but the high dose increased both hepatic lipid levels only in mPPARalpha mice. APFO increased mRNA and/or protein levels of PPARalpha target genes cytochrome P450 Cyp4a10, peroxisomal thiolase and bifunctional protein only in the liver of mPPARalpha mice, but not in Pparalpha-null or hPPARalpha mice. This chemical also increased expression of mitochondrial very long chain acyl-CoA dehydrogenase only in the liver of mPPARalpha mice. Taken together, human PPARalpha may be less responsive to PFOA than that of mice when a relatively low dose is applied. This information may be very valuable in considering whether PFOA influences the lipid metabolism in humans.
Keywords
Ammonium perflurooctanate; Peroxisome proliferator-activated receptor (PPAR) alpha; Humanized PPAR alpha mouse; Ppar alpha-null mouse; Lipid metabolism
Tags
•
Trichloroacetic acid (TCA) (Final, 2011)
PFAS
•
Additional PFAS (formerly XAgency)
•
Expanded PFAS SEM (formerly PFAS 430)
Litsearch: September 2019
PubMed
Not prioritized for screening
Potassium perfluorooctanoate
Sodium perfluorooctanoate
•
PFAS 150
Literature Search August 2019
PubMed
Web of Science
Ammonium perfluorooctanoate
Perfluorooctanoic acid
•
PFHxS
•
PFOA and PFOS OW MCLG Approaches
Cited in White Papers
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