Polybrominated Diphenyl Ethers Alter Hepatic Phosphoenolpyruvate Carboxykinase Enzyme Kinetics in Male Wistar Rats: Implications for Lipid and Glucose Metabolism

Xenobiotics such as phenobarbital, 2,3,7,8-tetrachlorodibenzo-p-dioxin, and Aroclor 1254 significantly suppress the activity of a key gluconeogenic and glyceroneogenic enzyme, phosphoenolpyruvate carboxykinase (PEPCK), suggesting that xenobiotics disrupt hepatic glucose and fat metabolism. The effects of polybrominated diphenyl ethers (PBDE), a family of synthetic flame-retardant chemicals, on PEPCK activity is unknown. This study investigated the effect of DE-71, a commercial PBDE mixture, on PEPCK enzyme kinetics. Forty-eight 1-mo-old male Wistar rats were gavaged daily with either corn oil or corn oil containing 14 mg/kg DE-71 for 3, 14, or 28 d (n = 8/group). At each time point, fasting plasma glucose, insulin, and C-peptide were measured and hepatic PEPCK activity, lipid content, and three cytochrome P-450 enzymes (CYP1A, -2B, and -3A) were assayed. PBDE treatment for 28 d significantly decreased PEPCK Vmax (μmol/min/g liver weight) by 43% and increased liver lipid by 20%, compared to control. CYP1A,...