EFFECT OF IN VIVO POLYBROMINATED DIPHENYL ETHER (PBDE) TREATMENT ON HEPATIC GLYCERONEOGENESIS AND LIPID METABOLISM

Polybrominated diphenyl ethers (PBDEs) are flame-retardant chemicals that contaminate the environment. Through ingestion and inhalation, these chemicals get into the human body, where they affect the liver by suppressing the metabolic enzyme phosphoenolpyruvate carboxykinase (PEPCK), which is partially responsible for glyceride-glycerol production via glyceroneogenesis. This study investigated the effects of PBDE-induced hepatic PEPCK suppression on glyceroneogenesis, and the associated perturbations in liver lipid metabolism. Twenty-eight male, weanling Wistar rats were treated daily with 14 mg/kg body weight PBDE mixture, DE-71 (TRT, n=14) or corn oil vehicle (CON, n=14) for 28 days. After a 48-hour fast, rats were sacrificed and blood and livers removed for analysis of serum metabolites, PEPCK protein levels, PEPCK activity, liver lipids, and glyceroneogenesis. TRT animals exhibited significant increases in serum ketones (27%), accompanied by significant decreases in serum triglycerides (27%), and liver PEPCK protein (23%), PEPCK Vmax (40%), lipids (29%), and glyceroneogenesis (41%) compared to CON. These findings demonstrate that PBDE-induced PEPCK suppression impacts liver lipid metabolism, likely by suppressing glyceroneogenesis