Polybrominated Diphenyl Ethers Alter Hepatic Phosphoenolpyruvate Carboxykinase Enzyme Kinetics in Male Wistar Rats: Implications for Lipid and Glucose Metabolism
Abstract
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 (mu mol/min/g liver weight) by 43% and increased liver lipid by 20%, compared to control. CYP1A, -2B, and -3A Vmax values were enhanced by 5-, 6-, and 39-fold, respectively, at both 14 and 28 d in treated rats compared to control. There was a significant inverse and temporal correlation between CYP3A and PEPCK Vmax for the treatment group. Fasting plasma glucose, insulin, and C-peptide levels were not markedly affected by treatment, but the glucose:insulin ratio was significantly higher in treated compared to control rats. Data suggest that in vivo PBDE treatment compromises liver glucose and lipid metabolism, and may influence whole-body insulin sensitivity.
Publication Date
1-1-2013
Journal Title
Journal of Toxicology and Environmental Health-Part A-Current Issues
Publisher
Taylor & Francis Group
Digital Object Identifier (DOI)
10.1080/15287394.2012.738457
Scientific Contribution Number
2487
Document Type
Article
Rights
©2013 Taylor & Francis Group
Recommended Citation
Nash, Jessica T.; Szabo, David T.; and Carey, Gale B., "Polybrominated Diphenyl Ethers Alter Hepatic Phosphoenolpyruvate Carboxykinase Enzyme Kinetics in Male Wistar Rats: Implications for Lipid and Glucose Metabolism" (2013). Journal of Toxicology and Environmental Health-Part A-Current Issues. 135.
https://scholars.unh.edu/nhaes/135