Transcriptome and Metabolome analysis reveal HFPO-TA induced disorders of hepatic glucose and lipid metabolism in rat by interfering with PPAR signaling pathway

Food Chem Toxicol. 2024 Jun:188:114632. doi: 10.1016/j.fct.2024.114632. Epub 2024 Apr 6.

Abstract

PFOA is one of the most representative compounds in the family of perfluorinated organic compounds. Due to its varying toxicity, alternatives to PFOA are beginning to emerge. HFPO-TA is an alternative for PFOA. It is currently unclear whether HFPO-TA affects glucose and lipid metabolism. In this study, rats were used as an animal model to investigate the effects of HFPO-TA on liver glucose and lipid metabolism. We found that HFPO-TA can affect glucose tolerance. Through omics analysis and molecular detection, it was found that HFPO-TA mainly affects the PPAR signaling pathway in the liver of rats, inhibiting liver glycolysis while promoting glucose production. HFPO-TA not only promotes the synthesis of fatty acids in the liver, but also promotes the breakdown of fatty acids, which ultimately leads to the disruption of hepatic glucose and lipid metabolism. The effects of HFPO-TA on metabolism are discussed in this paper to provide a reference for the risk assessment of this PFOA substitute.

Keywords: HFPO-TA (hexafluoropropylene oxide trimer acid); Liver injury; Metabolism; PPAR signaling pathway; Transcriptome and metabolome analysis.

MeSH terms

  • Animals
  • Fluorocarbons
  • Glucose* / metabolism
  • Lipid Metabolism* / drug effects
  • Liver* / drug effects
  • Liver* / metabolism
  • Male
  • Metabolome* / drug effects
  • Peroxisome Proliferator-Activated Receptors* / genetics
  • Peroxisome Proliferator-Activated Receptors* / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction* / drug effects
  • Transcriptome* / drug effects

Substances

  • Peroxisome Proliferator-Activated Receptors
  • Glucose
  • Fluorocarbons