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Adverse bioeffect of perfluorooctanoic acid on liver metabolic function in mice

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Perfluorooctanoic acid (PFOA), a kind of manufactured material, is widely accumulated around environmental system and into wildlife, including human beings. Toxicologically, PFOA induces hepatomegaly (liver enlargement) in the dose- and time-dependent manners. However, biological mechanism of hepatotoxicity warrants to be further investigated. In the present study, mature male mice were exposed to dosed PFOA for 21 days before conducting biochemical tests and immunoassays. As results, decreased fast blood glucose and elevated insulin contents were observed in PFOA-dosed mice. In addition, PFOA-dosed mice resulted in increased liver functional enzymes (GPT, GOT) in serum. And lipid contents (TG, lipoproteins) in serum and liver were changed abnormally. As shown in immunohistochemistry, increased insulin- and poly (ADP-ribose) polymerase (PARP)-positive cells were showed in PFOA-exposed pancreatic tissues. Moreover, CD36-positive cells were increased in PFOA-exposed livers, while ApoB-labeled cells were reduced. Further, immunoblot data showed that hepatocellular fibroblast growth factor 21 (FGF21) in PFOA-exposed liver was down-regulated dose-dependently. Taken together, our preliminary findings demonstrated that PFOA-induced hepatocellular lipotoxicity may be linked to impairing lipid-regulated proteins, as well as inducing insulin expression from pancreatic tissue.

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  1. Andersen LH, Miserez AR, Ahmad Z, Andersen RL (2016) Familial defective apolipoprotein B-100: A review. J Clin Lipidol 10(6):1297–1302. https://doi.org/10.1016/j.jacl.2016.09.009

  2. Botelho SC, Saghafian M, Pavlova S, Hassan M, DePierre JW, Abedi-Valugerdi M (2015) Complement activation is involved in the hepatic injury caused by high-dose exposure of mice to perfluorooctanoic acid. Chemosphere 129:225–231. https://doi.org/10.1016/j.chemosphere.2014.06.093

  3. Coskun T, Bina HA, Schneider MA, Dunbar JD, CC H, Chen Y, Moller DE, Kharitonenkov A (2008) Fibroblast growth factor 21 corrects obesity in mice. Endocrinology 149(12):6018–6027. https://doi.org/10.1210/en.2008-0816

  4. Ge B, Yang D, Wu X, Zhu J, Wei W, Yang B (2017) Cytoprotective effects of glycyrrhetinic acid liposome against cyclophosphamide-induced cystitis through inhibiting inflammatory stress. Int Immunopharmacol 54:139–144. https://doi.org/10.1016/j.intimp.2017.11.010

  5. Grijalva J, Vakili K (2013) Neonatal liver physiology. Semin Pediatr Surg 22(4):185–189. https://doi.org/10.1053/j.sempedsurg.2013.10.006

  6. Guo C, Pan Q, Su M, Li R (2017) Clinical immunophenotype of nasopharyngeal neuroendocrine carcinoma with metastatic liver cancer. Clin Chim Acta 471:283–285. https://doi.org/10.1016/j.cca.2017.06.016

  7. Hajri T, Han XX, Bonen A, Abumrad NA (2002) Defective fatty acid uptake modulates insulin responsiveness and metabolic responses to diet in CD36-null mice. J Clin Invest 109(10):1381–1389. https://doi.org/10.1172/JCI0214596

  8. Herceg Z, Wang ZQ (2001) Functions of poly(ADP-ribose) polymerase (PARP) in DNA repair, genomic integrity and cell death. Mutat Res 477(1-2):97–110. https://doi.org/10.1016/S0027-5107(01)00111-7

  9. Li R, Song J, Wu W, Wu X, Su M (2016) Puerarin exerts the protective effect against chemical induced dysmetabolism in rats. Gene 595(2):168–174. https://doi.org/10.1016/j.gene.2016.09.036

  10. Li R, Liang L, Wu X, Ma X, Su M (2017a) Valproate acid (VPA)-induced dysmetabolic function in clinical and animal studies. Clin Chim Acta 468:1–4. https://doi.org/10.1016/j.cca.2017.01.030

  11. Li R, Guo C, Wu X, Huang Z, Chen J (2017b) FGF21 functions as a sensitive biomarker of APAP-treated patients and mice. Oncotarget 8(27):44440–44446. 10.18632/oncotarget.17966

  12. Li K, Gao P, Xiang P, Zhang X, Cui X, Ma LQ (2017c) Molecular mechanisms of PFOA-induced toxicity in animals and humans: implications for health risks. Environ Int 99:43–54. https://doi.org/10.1016/j.envint.2016.11.014

  13. Mostafalou S (2016) Persistent organic pollutants and concern over the link with insulin resistance related metabolic diseases. Rev Environ Contam Toxicol 238:69–89. https://doi.org/10.1007/398_2015_5001

  14. Nakayama S, Harada K, Inoue K, Sasaki K, Seery B, Saito N, Koizumi A (2005) Distributions of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) in Japan and their toxicities. Environ Sci 12(6):293–313

  15. Oliaei F, Kriens D, Weber R, Watson A (2013) PFOS and PFC releases and associated pollution from a PFC production plant in Minnesota (USA). Environ Sci Pollut Res Int 20(4):1977–1992. https://doi.org/10.1007/s11356-012-1275-4

  16. Quist EM, Filgo AJ, Cummings CA, Kissling GE, Hoenerhoff MJ, Fenton SE (2015) Hepatic mitochondrial alteration in CD-1 mice associated with prenatal exposures to low doses of Perfluorooctanoic acid (PFOA). Toxicol Pathol 43(4):546–557. https://doi.org/10.1177/0192623314551841

  17. Rosen MB, Das KP, Rooney J, Abbott B, Lau C, Corton JC (2017) PPARα-independent transcriptional targets of perfluoroalkyl acids revealed by transcript profiling. Toxicology 387:95–107. https://doi.org/10.1016/j.tox.2017.05.013

  18. Staiger H, Keuper M, Berti L, Hrabe de Angelis M, Häring HU (2017) Fibroblast growth factor 21-metabolic role in mice and men. Endocr Rev 38(5):468–488. https://doi.org/10.1210/er.2017-00016

  19. Sugimoto T, Sato M, Dehle FC, Brnabic AJ, Weston A, Burge R (2016) Lifestyle-related metabolic disorders, osteoporosis, and fracture risk in Asia: a systematic review. Value Health Reg Issues 9:49–56. https://doi.org/10.1016/j.vhri.2015.09.005

  20. Woo YC, Xu A, Wang Y, Lam KS (2013) Fibroblast growth factor 21 as an emerging metabolic regulator: clinical perspectives. Clin Endocrinol 78(4):489–496. https://doi.org/10.1111/cen.12095

  21. Wu K, Guo C, Su M, Wu X, Li R (2017a) Biocharacterization of heat shock protein 90 in acetaminophen-treated livers without conspicuous drug induced liver injury. Cell Physiol Biochem 43(4):1562–1570. https://doi.org/10.1159/000482003

  22. Wu X, Liang M, Yang Z, Su M, Yang B (2017b) Effect of acute exposure to PFOA on mouse liver cells in vivo and in vitro. Environ Sci Pollut Res Int 24(31):24201–24206. https://doi.org/10.1007/s11356-017-0072-5

  23. Yang Q, Guo X, Sun P, Chen Y, Zhang W, Gao A (2017) Association of serum levels of perfluoroalkyl substances (PFASs) with the metabolic syndrome (MetS) in Chinese male adults: A cross-sectional study. Sci Total Environ (17)32778-X

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This study is granted in part by a funding from National Natural Science Foundation of Guangxi (2016GXNSFAA380081).

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Correspondence to Bin Yang.

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All laboratory mice were fed and handled in accordance with the Guidelines and Regulations of Department of Health in Guilin Medical University. These protocols were authorized by the Committee on the Use of Animal Subjects of the Guilin Medical University.

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The authors declare that they have no conflict of interest.

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Responsible editor: Philippe Garrigues

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Wu, X., Xie, G., Xu, X. et al. Adverse bioeffect of perfluorooctanoic acid on liver metabolic function in mice. Environ Sci Pollut Res 25, 4787–4793 (2018). https://doi.org/10.1007/s11356-017-0872-7

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  • PFOA
  • Lipids
  • Liver
  • Pancreas
  • Metabolism