The Ubiquitous Environmental Pollutant Perfluorooctanoicacid Inhibits Feeding Behavior via Peroxisome Proliferator-Activated Receptor-α
Open accessAbstract
Perfluorinated compounds (PFCs) have been employed as surface treatment agents in a variety of products. Perfluorooctanoic acid (PFOA), a PFC that is found globally in the environment and in human tissues, has been increasing significantly in serum levels over the past 50 years. Here, we demonstrated that PFOA inhibits feeding behavior as potently as the endogenous peroxisome proliferator-activated receptor (PPAR)-alpha ligand, oleoylethanolamide (OEA), via the activation of PPAR-alpha, the vagal nerve and hypothalamic neuropeptides. Peripherally administered PFOA decreased food intake as potently as OEA. PFOA decreased gastric emptying and increased the expression level of the gene encoding urocortin 1 in the hypothalamus and the immunoreaction for urocortin 1 in the paraventricular nucleus. Vagotomy attenuated the inhibitory effects of PFOA on feeding. The inhibition of food intake and body-weight gain by PFOA was completely mitigated in PPAR-alpha-/-mice. Our studies demonstrated that the ubiquitous environmental pollutant PFOA works as an imitator of OEA mimicking its action in the feeding regulatory system, providing a new mode of action as represented by environmental 'anorexigens'.
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Asakawa et al. (2008) saw an increase in hypothalamic paraventricular nucleus concentrations of urocortin 1 in mice exposed to PFOA.
“they saw an increase in hypothalamic paraventricular nucleus (PVN) concentrations of an endogenous ligand that has been shown to attenuate feeding and gastric motility, urocortin 1, in mice exposed to PFOA (Asakawa et al., 2008).”
From A Critical Review and Meta-Analysis of Impacts of Per- and Polyfluorinated Substances on the Brain and Behavior (2022) · cites this paper as Asakawa et al., 2008
The Results report increased urocortin 1 immunoreactivity in the PVN of PFOA-treated mice compared with controls. The paper did not measure urocortin 1 concentrations in the PVN, so the claim is more specific than the reported finding. (LLM, conf=0.85)
Experimental — accuracy not yet measuredPPARα is expressed in the paraventricular nucleus of the hypothalamus, where it plays a role in the feedback system that regulates feeding behavior.
“PPARα is expressed in the PVN of the hypothalamus, where it plays a role in the feedback system that regulates feeding behavior (Asakawa et al., 2008).”
From A Critical Review and Meta-Analysis of Impacts of Per- and Polyfluorinated Substances on the Brain and Behavior (2022) · cites this paper as Asakawa et al., 2008
The Discussion reports that PFOA’s effect on feeding depends on PPARα and that anorexigenic signals reach the PVN. The Results identify increased urocortin 1—not PPARα—in the PVN. Our copy does not establish that PPARα is expressed there or plays a feedback role there; page numbers are unavailable in the indexed passages. (LLM, conf=0.88)
Experimental — accuracy not yet measuredA follow-up study by Asakawa et al. (2008) examining PFOA administered via intraperitoneal injection yielded similar findings with decreases in food intake and delayed gastric emptying.
“A follow up study by Asakawa et al. (2008) examining the activity of PFOA on mice, administered via intraperitoneal (IP) injection, yielded similar findings with decreases in food intake and delayed gastric emptying.”
From A Critical Review and Meta-Analysis of Impacts of Per- and Polyfluorinated Substances on the Brain and Behavior (2022) · cites this paper as Asakawa et al., 2008
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- Authors
- Asakawa, A., Toyoshima, M., Harada, K., Fujimiya, M., Inoue, K., & Koizumi, A.
- Affiliations
- Kyoto University (JP)
- Shiga University of Medical Science (JP)
- Corresponding author
- Koizumi, Akio
- Venue
- International Journal of Molecular Medicine
- Publisher
- Spandidos Publications
- Published
- 2008-04-01
- Volume
- 21
- Issue
- 4
- Pages
- 439-45
- ISSN
- 1107-3756 (ISSN-L)
- 1791-244X
- OpenAlex
- W2091333653
- Cited by
- 26
- References
- 23
- Citations by year
- 2025: 1 · 2024: 1 · 2022: 1 · 2019: 1 · 2017: 2 · 2016: 1 · 2015: 2 · 2014: 2 · 2013: 2 · 2012: 2
- FWCI
- 2.68
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- International Journal of Molecular Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Physical Sciences › Environmental Science › Environmental Chemistry › Per- and polyfluoroalkyl substances research
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- perfluorooctanoic acid, perfluorinated compounds, PPARα, feeding behavior, dietary intake, oleoylethanolamide, vagus nerve, hypothalamic neuropeptides, urocortin 1, paraventricular nucleus, gastric emptying, weight gain, environmental pollutants
- MeSH terms
- Animals, Base Sequence, Caprylates, Eating, Environmental Pollutants, Feeding Behavior, Female, Fluorocarbons, Food Deprivation, Gastric Emptying, Humans, Hypothalamus, Male, Paraventricular Hypothalamic Nucleus, RNA, Messenger, Vagotomy, DNA Primers, Mice, Knockout, PPAR alpha, Mice, Urocortins
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