Polybrominated Diphenyl Ether (PBDE)-Induced Suppression of Phosphoenolpyruvate Carboxykinase (PEPCK) Decreases Hepatic Glyceroneogenesis and Disrupts Hepatic Lipid Homeostasis.

Academic Article


  • Polybrominated diphenyl ethers (PBDE) are a class of flame-retardant chemicals that leach into the environment and enter the human body. PBDE have been shown to suppress activity of phosphoenolpyruvate carboxykinase (PEPCK), a key enzyme in fatty acid esterification via hepatic glyceroneogenesis. The objective of this investigation was to assess hepatic glyceroneogenesis and lipid metabolism in PBDE-treated rats. Male, weanling Wistar rats were gavaged daily for 28 d with 14 mg/kg body weight of either DE-71, a commercial PBDE mixture (treated), or corn oil (control). After a 48-h fast, rats were euthanized, blood was obtained, and livers were excised. Suppression of hepatic PEPCK activity by 40% was noted. Serum ketone bodies were elevated by 27% in treated rats compared to controls, while hepatic glyceroneogenesis as measured by (14)C-pyruvate incorporation into triglycerides was 41% lower in explants from treated rats compared to controls. Liver lipid content was 29% lower in treated animals compared to controls. Taken together, these findings suggest that DE-71-induced inhibition of hepatic PEPCK activity alters lipid metabolism by redirecting fatty acids away from esterification and storage toward ketone synthesis.
  • Authors

  • Cowens, Kylie R
  • Simpson, Stephen
  • Thomas, W. Kelley
  • Carey, Gale B
  • Status

    Publication Date

  • 2015
  • Keywords

  • Animals
  • Environmental Pollutants
  • Flame Retardants
  • Glycerophosphates
  • Halogenated Diphenyl Ethers
  • Homeostasis
  • Intracellular Signaling Peptides and Proteins
  • Lipid Metabolism
  • Liver
  • Male
  • Phosphoenolpyruvate Carboxykinase (GTP)
  • Rats
  • Rats, Wistar
  • Triglycerides
  • Digital Object Identifier (doi)

    Pubmed Id

  • 26692069
  • Start Page

  • 1437
  • End Page

  • 1449
  • Volume

  • 78
  • Issue

  • 23-24