Perfluorooctanoic Acid Induces Liver Lipid Metabolic Disorder In Mice

Aims: Perfluorooctanoic acid(PFOA)is a synthetic environmental pollutant,mainly used as an additive for non-stick materials and widely used in industrial production and consumer consumption.PFOA has a good stability.It is extremely difficult to degrade and can be widely accumulated in ecosystems and mammals.PFOA also can be transmitted and bio-enriched in the food chain.In toxicology,PFOA can induce liver enlargement,resulting in disorder of lipid metabolism in liver tissue cells,but the specific molecular mechanism remains unknown.Therefore,this experiment is mainly aimed at the study of liver lipid toxicity caused by PFOA.More importantly,it explains the possible molecular mechanisms and provides scientific ideas for the development of drugs for the treatment of disorders of liver lipid metabolism caused by environmental pollutants.Methods: Twenty-four adult male Kunming mice were randomly divided into three groups(n=8): control group,low dose group of PFOA(1 mg/kg),high dose group of PFOA(5 mg/kg).After 21 days of experiment,blood samples and liver pancreas specimens were collected for biochemical detection,immunostaining and immunoblotting analysis to evaluate the effects of PFOA on liver and pancreatic cell function and lipid metabolism in mice.Results: 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(P<0.05).And lipid contents(TG,lipoproteins)in serum and liver were changed abnormally(P<0.05).As shown in immunohistochemistry,increased insulinand 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 Apo B-labeled cells were reduced.Further,immunoblot data showed that hepatocellular fibroblast growth factor 21(FGF21)in PFOA-exposed liver was down-regulated dose-dependently(P<0.05).Conclusion: Hepatocyte lipotoxicity induced by PFOA may be associated with impaired lipid-regulated "into-out" pathways and induction of insulin secretion disorders in pancreatic cells.