TY - JOUR AB - Dioxins and dioxin-like compounds encompass a group of structurally related heterocyclic compounds that bind to and activate the aryl hydrocarbon receptor (AhR). The prototypical dioxin is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a highly toxic industrial byproduct that incites numerous adverse physiological effects. Global commercial production of the structurally similar polychlorinated biphenyls (PCBs), however, commenced early in the 20(th) century and continued for decades; dioxin-like PCBs therefore contribute significantly to total dioxin-associated toxicity. In this study, PCB 126, the most potent dioxin-like PCB, was evaluated with respect to its direct effects on hepatic glucose metabolism using primary mouse hepatocytes. Overnight treatment with PCB 126 reduced hepatic glycogen stores in a dose-dependent manner. Additionally, PCB 126 suppressed forskolin-stimulated gluconeogenesis from lactate. These effects were independent of acute toxicity, as PCB 126 did not increase lactate dehydrogenase release nor affect lipid metabolism or total intracellular ATP. Interestingly, provision of cells with glycerol instead of lactate as the carbon source completely restored hepatic glucose production, indicating specific impairment in the distal arm of gluconeogenesis. In concordance with this finding, PCB 126 blunted the forskolin-stimulated increase in phosphoenolpyruvate carboxykinase (PEPCK) mRNA levels without affecting glucose-6-phosphatase expression. Myricetin, a putative competitive AhR antagonist, reversed the suppression of PEPCK induction by PCB 126. Furthermore, other dioxin-like PCBs demonstrated similar effects on PEPCK expression in parallel with their ability to activate AhR. It therefore appears that AhR activation mediates the suppression of PEPCK expression by dioxin-like PCBs, suggesting a role for these pollutants as disruptors of energy metabolism. AD - Department of Medicine, Kovler Center for Biomedical Discovery, The University of Chicago, Chicago, Illinois, United States of America. AN - 22615911 AU - Zhang, W. AU - Sargis, R. M. AU - Volden, P. A. AU - Carmean, C. M. AU - Sun, X. J. AU - Brady, M. J. DO - 10.1371/journal.pone.0037103 ET - 2012/05/23 J2 - PloS one LA - eng M1 - 5 N1 - Zhang, Wenshuo Sargis, Robert M Volden, Paul A Carmean, Christopher M Sun, Xiao J Brady, Matthew J PLoS One. 2012;7(5):e37103. Epub 2012 May 16. PY - 2012 SN - 1932-6203 (Electronic) 1932-6203 (Linking) SP - e37103 ST - PCB 126 and Other Dioxin-Like PCBs Specifically Suppress Hepatic PEPCK Expression via the Aryl Hydrocarbon Receptor T2 - PLoS One TI - PCB 126 and Other Dioxin-Like PCBs Specifically Suppress Hepatic PEPCK Expression via the Aryl Hydrocarbon Receptor UR - http://www.ncbi.nlm.nih.gov/pubmed/22615911 VL - 7 ID - 131 ER -