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Cited by 110Per- and polyfluoroalkyl substances researchPeroxisome Proliferator-Activated ReceptorsToxic Organic Pollutants Impact

Perfluorooctanoic acid exposure for 28 days affects glucose homeostasis and induces insulin hypersensitivity in mice

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Yan, Shengmin, Zhang, Hongxia, Zheng, Fei, Sheng, Nan, Guo, Xuejiang, Dai, Jiayin·2015·Scientific Reports
DOI 10.1038/srep11029PMC PMC4464286
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Abstract

Perfluoroalkyl acids (PFAAs) are widely used in many applications due to their unique physical and chemical characteristics. Because of the increasing prevalence of metabolic syndromes, including obesity, dyslipidemia and insulin resistance, concern has arisen about the roles of environmental pollutants in such diseases. Earlier epidemiologic studies showed a potential association between perfluorooctanoic acid (PFOA) and glucose metabolism, but how PFOA influences glucose homeostasis is still unknown. Here, we report on the modulation of the phosphatidylinositol 3-kinase-serine/threonine protein kinase (PI3K-AKT) signaling pathway in the livers of mice after 28 d of exposure to PFOA. Compared with normal mice, PFOA exposure significantly decreased the expression of the phosphatase and tensin homologue (PTEN) protein and affected the PI3K-AKT signaling pathway in the liver. Tolerance tests further indicated that PFOA exposure induced higher insulin sensitivity and glucose tolerance in mice. Biochemical analysis revealed that PFOA exposure reduced hepatic glycogen synthesis, which might be attributed to gluconeogenesis inhibition. The levels of several circulating proteins were altered after PFOA exposure, including proteins potentially related to diabetes and liver disease. Our results suggest that PFOA affected glucose metabolism and induced insulin hypersensitivity in mice.

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  • Animal experiments have demonstrated that exposure to PFASs can induce metabolic disturbance and IR through inflammatory response and endocrine disruption, resulting in an increased incidence of T2D.

    “Animal experiments have also demonstrated that exposure to PFASs can induce metabolic disturbance and IR through inflammatory response and endocrine disruption, resulting in an increased incidence of T2D (Dong et al., 2022; Fang et al., 2012; Yan et al., 2015).”

    From Exposure to per- and polyfluoroalkyl substances in early pregnancy, risk of gestational diabetes mellitus, potential pathways, and influencing factors in pregnant women: A nested case-control study (2023) · cites this paper as Yan et al., 2015

    The Results (‘PFOA exposure induced insulin hypersensitivity in mice’) report increased insulin sensitivity in liver and muscle, not insulin resistance. The Discussion says this hypersensitivity could help defend against type 2 diabetes, contrary to the attributed increase in diabetes incidence. The study does report disturbed glucose metabolism, but these passages do not establish the claimed inflammatory or endocrine mechanism. (LLM, conf=0.89)

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Cited by

Sorted by citations

Authors
Yan, S., Zhang, H., Zheng, F., Sheng, N., Guo, X., & Dai, J.
Affiliations
  • Chinese Academy of Sciences (CN)
  • Shanxi Agricultural University (CN)
  • State Key Laboratory of Reproductive Medicine (CN)
Corresponding author
Dai, Jiayin
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2015-06-12
Volume
5
Issue
1
Pages
11029-11029
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/srep11029
PMC
PMC4464286
OpenAlex
W592541448
Cited by
110
References
6
Citations by year
2026: 5 · 2025: 13 · 2024: 15 · 2023: 11 · 2022: 13 · 2021: 16 · 2020: 10 · 2019: 3 · 2018: 8 · 2017: 7 · 2016: 7 · 2015: 1 · 2013: 1
FWCI
5.65
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • National Natural Science Foundation of China (XDB14040202, 31320103915, 21277143, 31025006)
  • Chinese Academy of Sciences (31320103915, XDB14040202)
Topics
  • Physical Sciences › Environmental Science › Environmental Chemistry › Per- and polyfluoroalkyl substances research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
Keywords
perfluorooctanoic acid, glucose homeostasis, insulin hypersensitivity, glucose tolerance, PI3K/Akt signaling, PTEN, hepatic glycogen synthesis, gluconeogenesis, liver, environmental pollutants, metabolic syndrome, diabetes mellitus
MeSH terms
Animals, Caprylates, Drug Hypersensitivity, Fluorocarbons, Glucose, Glycogen, Homeostasis, Insulin, Liver, Male, Mice, Inbred BALB C, Time Factors, Signal Transduction, Phosphatidylinositol 3-Kinases, Proto-Oncogene Proteins c-akt, PTEN Phosphohydrolase, Mice

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