Data from: PCB126 inhibits the activation of AMPK-CREB signal transduction required for energy sensing in liver

3,3’,4,4’,5-pentachlorobiphenyl (PCB126), a dioxin-like PCB, elicits
toxicity through a wide array of non-carcinogenic effects, including
metabolic syndrome, wasting, and non-alcoholic fatty-liver disease
(NAFLD). 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 d, prior
euthanasia. A subset of rats from each group were fasted for 12h (vehicle
(n=6) and PCB126 (n=4)). Rats only showed significant weight loss between
days 14 and 28 (P<0.05) and some mortality (P=0.0413). 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 gluconeogenic substrates, exacerbating the
hypoglycemia. Additionally, PCB126 caused hepatic steatosis and decreased
the expression of the transcription factor Pparα and its targets,
necessary for fatty-acid oxidation. The observed metabolic disruption
across multiple branches of fasting metabolism resulted from inhibition in
the activation of enzyme AMPK and transcription factor CREB signaling,
necessary for “sensing” energy-deprivation and the induction of enzymes
that respond to the PCB126 triggered fuel crisis in liver.