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

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.