Figure 5

Cellular pathways potentially involved in X. tropicalis hepatocyte responses to BaP exposure at sub-lethal concentration. This model, based on our transcriptome and liver phenotype dynamic analyses, suggests that BaP is responsible for the induction of an insulin-resistance-like phenotype in Xenopus. Insulin resistance is characterized by the over-transcription of gluconeogenic enzymes genes (PEPCK), sustained hyperglycemia, an over-transcription of glucose transporter (GLUT2) and severe liver steatosis. Consequently, hyperinsulinemia may lead to the marked induction of cholesterol synthesis pathways and to a decrease in cholesterol export to the bile. The accumulation of lipids and cholesterol in the hepatocytes thus induces both ER stress and lipid toxicity leading to apoptosis or necrosis. LDL, Low density lipoprotein; LDLR, Low density lipoprotein receptor; GLUT2, Glucose transporter 2; Glc, glucose; Chol, cholesterol; PEPCK, phosphoenolpyruvate carboxykinase 1; HMGCoAR, 3-hydroxy-3-methylglutaryl-CoA reductase; SREBP-TF2, sterol regulatory element binding transcription factor 2; ER, endoplasmic reticulum; FFA, Free fatty acid, TG, triglycerides; Insulin R, insulin resistance.