PMID- 37236338
OWN - NLM
STAT- MEDLINE
DCOM- 20230616
LR  - 20230627
IS  - 1879-3185 (Electronic)
IS  - 0300-483X (Linking)
VI  - 493
DP  - 2023 Jul
TI  - PFOA exposure induces aberrant glucose and lipid metabolism in the rat liver 
      through the AMPK/mTOR pathway.
PG  - 153551
LID - S0300-483X(23)00137-3 [pii]
LID - 10.1016/j.tox.2023.153551 [doi]
AB  - Perfluorooctanoic acid (PFOA) is the most prominent member of a widely utilized 
      family of compounds named Perfluoroalkyl substances (PFASs). Initially produced 
      for use in both industrial and consumer applications, it has since been 
      recognized that PFASs are extremely persistent in the environment where they have 
      been characterized as persistent organic pollutants (POPs). While previous 
      studies have demonstrated that PFOA may induce disorders of lipid and 
      carbohydrate metabolism, the precise mechanisms by which PFOA produces this 
      phenotype and the involvement of downstream AMPK/mTOR pathways remains unclear. 
      In this study, male rats were exposed to 1.25, 5 and 20 mg PFOA/kg body 
      weight/day for 28 days by oral gavage. After 28 days, blood was collected and 
      tested for serum biochemical indicators and livers were removed and weighed. To 
      investigate aberrant metabolism in rats exposed to PFOA, livers were analyzed by 
      performing LC-MS/MS untargeted metabolomics, quantitative real-time PCR, western 
      blotting, immunohistochemical staining was also performed on exposed tissues. Our 
      results showed that exposure to PFOA induced liver damage, increased the 
      expression of glucose and lipid related biochemical indexes in liver and serum, 
      and altered the expression levels of AMPK/mTOR pathway related genes and 
      proteins. In summary, this study clarifies the mechanisms responsible for PFOA 
      toxicity in the liver of exposed animals.
CI  - Copyright (c) 2023 Elsevier B.V. All rights reserved.
FAU - Zhang, Xuemin
AU  - Zhang X
AD  - Anhui Province Key Laboratory of Immunology in Chronic Diseases, Bengbu Medical 
      College, Bengbu 233030, PR China; Department of Biochemistry and Molecular 
      Biology, School of Laboratory Medicine, Bengbu Medical College, Bengbu 233030, PR 
      China; Bengbu Medical College Key Laboratory of Cancer Research and Clinical 
      Laboratory Diagnosis, School of Laboratory Medicine, Bengbu Medical College, 
      Bengbu 233030, PR China.
FAU - Ren, Xijuan
AU  - Ren X
AD  - School of Public Health, Bengbu Medical College, Bengbu 233030, PR China.
FAU - Sun, Weiqiang
AU  - Sun W
AD  - Anhui Province Key Laboratory of Immunology in Chronic Diseases, Bengbu Medical 
      College, Bengbu 233030, PR China; Department of Biochemistry and Molecular 
      Biology, School of Laboratory Medicine, Bengbu Medical College, Bengbu 233030, PR 
      China; Bengbu Medical College Key Laboratory of Cancer Research and Clinical 
      Laboratory Diagnosis, School of Laboratory Medicine, Bengbu Medical College, 
      Bengbu 233030, PR China.
FAU - Griffin, Nathan
AU  - Griffin N
AD  - Department of Cell and Tissue Biology, University of California, San Francisco, 
      CA, USA.
FAU - Wang, Li
AU  - Wang L
AD  - School of Public Health, Bengbu Medical College, Bengbu 233030, PR China. 
      Electronic address: wangli@bbmc.edu.cn.
FAU - Liu, Hui
AU  - Liu H
AD  - Anhui Province Key Laboratory of Immunology in Chronic Diseases, Bengbu Medical 
      College, Bengbu 233030, PR China; Department of Biochemistry and Molecular 
      Biology, School of Laboratory Medicine, Bengbu Medical College, Bengbu 233030, PR 
      China; Bengbu Medical College Key Laboratory of Cancer Research and Clinical 
      Laboratory Diagnosis, School of Laboratory Medicine, Bengbu Medical College, 
      Bengbu 233030, PR China. Electronic address: liuhui@bbmc.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230524
PL  - Ireland
TA  - Toxicology
JT  - Toxicology
JID - 0361055
RN  - 947VD76D3L (perfluorooctanoic acid)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - IY9XDZ35W2 (Glucose)
RN  - 0 (Caprylates)
RN  - 0 (Fluorocarbons)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.1.1 (mTOR protein, rat)
SB  - IM
MH  - Male
MH  - Rats
MH  - Animals
MH  - *Lipid Metabolism
MH  - AMP-Activated Protein Kinases/metabolism
MH  - Glucose/metabolism
MH  - Chromatography, Liquid
MH  - Tandem Mass Spectrometry
MH  - Caprylates/toxicity
MH  - Liver/metabolism
MH  - *Fluorocarbons/toxicity/metabolism
MH  - TOR Serine-Threonine Kinases/metabolism
OTO - NOTNLM
OT  - AMPK/mTOR
OT  - Liver injury
OT  - Metabolism
OT  - Perfluorooctanoic acid (PFOA)
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2023/05/27 09:42
MHDA- 2023/06/16 06:42
CRDT- 2023/05/26 19:24
PHST- 2023/02/13 00:00 [received]
PHST- 2023/05/05 00:00 [revised]
PHST- 2023/05/19 00:00 [accepted]
PHST- 2023/06/16 06:42 [medline]
PHST- 2023/05/27 09:42 [pubmed]
PHST- 2023/05/26 19:24 [entrez]
AID - S0300-483X(23)00137-3 [pii]
AID - 10.1016/j.tox.2023.153551 [doi]
PST - ppublish
SO  - Toxicology. 2023 Jul;493:153551. doi: 10.1016/j.tox.2023.153551. Epub 2023 May 
      24.