PCB126 Inhibits the Activation of AMPK-CREB Signal Transduction Required for Energy Sensing in Liver

Toxicological Sciences : an Official Journal of the Society of Toxicology
Gopi S GadupudiLarry W Robertson

Abstract

3,3',4,4',5-pentachlorobiphenyl (PCB126), a dioxin-like PCB, elicits toxicity through a wide array of noncarcinogenic effects, including metabolic syndrome, wasting, and nonalcoholic fatty-liver disease. Previously, we reported decreases in the transcription of several enzymes involved in gluconeogenesis, before the early onset of lipid accumulation. Hence, this study was aimed at understanding the impact of resultant decreases gluconeogenic enzymes on growth, weight, and metabolism in the liver, upon extended exposure. Male Sprague Dawley rats (75-100 g), fed a defined AIN-93G diet, were injected (ip) with single dose of soy oil (5 ml/kg body weight; n = 14) or PCB126 (5 µmol/kg; n = 15), 28 days, prior euthanasia. A subset of rats from each group were fasted for 12 h (vehicle [n = 6] and PCB126 [n = 4]). Rats only showed significant weight loss between days 14 and 28 (p < .05) and some mortality (p = .0413). As in our previous studies, the expression levels of enzymes involved in gluconeogenesis (Pepck-c, G6Pase, Sds, Pc, and Ldh-A) and glycogenolysis (Pygl) were strongly downregulated. The decreased expression of these enzymes in PCB126-treated rats after a 12 h fast decreased hepatic glucose production from glycogen and glu...Continue Reading

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Citations

Nov 24, 2018·Environmental Science and Pollution Research International·Camille Tremblay-LaganièreCéline Aguer
May 28, 2019·Current Environmental Health Reports·Banrida WahlangMatthew C Cave
Oct 30, 2020·Diabetes, Metabolic Syndrome and Obesity : Targets and Therapy·Qiuli ShanJing Guo
Apr 27, 2019·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Banrida WahlangMatthew C Cave
Jul 14, 2021·Toxicology and Applied Pharmacology·Violet KlenovAileen F Keating

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