Lipid accumulation responses in the liver of Rana nigromaculata induced by perfluorooctanoic acid (PFOA)

Ecotoxicol Environ Saf. 2019 Jan 15;167:29-35. doi: 10.1016/j.ecoenv.2018.09.120. Epub 2018 Oct 4.

Abstract

Perfluorooctanoic acid (PFOA) is a perfluorinated compound that is widely distributed, is persistent in the environment, and has a low-level chronic exposure effect on human health. The aim of this study was to investigate the peroxisome proliferator activated receptors γ (PPARγ) and the sterol regulatory element-binding protein 2 (SREBP2) signaling pathways in regulating the lipid damage response to PFOA in the livers of amphibians. Male and female frogs (Rana nigromaculata) were exposed to 0, 0.01, 0.1, 0.5 and 1 mg/L PFOA. After treatment, we evaluated the pathological changes in the liver by Oil Red O, staining and examined the total cholesterol (T-CHO) and triglyceride (TG) contents. The mRNA expression levels of PPARγ, Fatty acid synthase (FAS), Acetyl-CoA carboxylase (ACC), Glycerol-3-phosphate acyltransferase (GPAT), SREBP2 and 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The administration of PFOA caused marked lipid accumulation damage in the amphibian livers. The T-CHO contents were elevated significantly after PFOA treatment; these results show a dose-dependent manner in both sexes. The TG content showed a significant increase in male livers, while it was elevated significantly in female livers. The RT-PCR results showed that the mRNA expression levels of PPARγ, ACC, FAS, GPAT, SREBP2 and HMG-CoA were significantly dose-dependently increased in the PFOA-treated groups compared with those of the control group. Our results demonstrated that PFOA-induced lipid accumulation also affected the expression levels of genes FAS, ACC, GPAT and HMG-CoA in the PPARγ and SREBP2 signaling pathways in the liver. These finding will provide a scientific theoretical basis for the protection of Rana nigromaculata against PFOA effects.

Keywords: Lipid accumulation; Liver; PFOA; PPARγ; Rana nigromaculata.

MeSH terms

  • Acyl Coenzyme A / metabolism
  • Animals
  • Caprylates / toxicity*
  • Cholesterol / metabolism
  • Dose-Response Relationship, Drug
  • Fatty Acid Synthases / genetics
  • Fatty Acid Synthases / metabolism
  • Female
  • Fluorocarbons / toxicity*
  • Lipid Metabolism / drug effects*
  • Liver / drug effects*
  • Liver / metabolism
  • Male
  • PPAR gamma / genetics
  • PPAR gamma / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Ranidae / metabolism*
  • Sterol Regulatory Element Binding Protein 2 / genetics
  • Sterol Regulatory Element Binding Protein 2 / metabolism
  • Triglycerides / metabolism

Substances

  • Acyl Coenzyme A
  • Caprylates
  • Fluorocarbons
  • PPAR gamma
  • RNA, Messenger
  • Sterol Regulatory Element Binding Protein 2
  • Triglycerides
  • 3-hydroxy-3-methylglutaryl-coenzyme A
  • perfluorooctanoic acid
  • Cholesterol
  • Fatty Acid Synthases