Upregulation of fatty acid synthesis genes in the livers of adolescent female rats caused by inhalation exposure to PCB52 (2,2',5,5'-Tetrachlorobiphenyl)

Environ Toxicol Pharmacol. 2024 Sep:110:104520. doi: 10.1016/j.etap.2024.104520. Epub 2024 Jul 25.

Abstract

Elevated airborne PCB levels in older schools are concerning due to their health impacts, including cancer, metabolic dysfunction-associated steatotic liver disease (MASLD), cardiovascular issues, neurodevelopmental diseases, and diabetes. During a four-week inhalation exposure to PCB52, an air pollutant commonly found in school environments, adolescent rats exhibited notable presence of PCB52 and its hydroxylated forms in their livers, alongside changes in gene expression. Female rats exhibited more pronounced changes in gene expression compared to males, particularly in fatty acid synthesis genes regulated by the transcription factor SREBP1. In vitro studies with human liver cells showed that the hydroxylated metabolite of PCB52, 4-OH-PCB52, but not the parent compound, upregulated genes involved in fatty acid biosynthesis similar to in vivo exposure. These findings highlight the sex-specific effects of PCB52 exposure on livers, particularly in females, suggesting a potential pathway for increased MASLD susceptibility.

Keywords: Fatty acid synthesis; Inhalation exposure; PCB52; Persistent organic pollutant; Polychlorinated biphenyl; Steatosis.

MeSH terms

  • Air Pollutants / toxicity
  • Animals
  • Fatty Acids* / metabolism
  • Female
  • Humans
  • Inhalation Exposure*
  • Liver* / drug effects
  • Liver* / metabolism
  • Male
  • Polychlorinated Biphenyls* / toxicity
  • Rats
  • Rats, Sprague-Dawley
  • Sterol Regulatory Element Binding Protein 1 / genetics
  • Sterol Regulatory Element Binding Protein 1 / metabolism
  • Up-Regulation* / drug effects

Substances

  • Polychlorinated Biphenyls
  • Fatty Acids
  • Air Pollutants
  • Sterol Regulatory Element Binding Protein 1