Introducing a new pre-clinical rat model of advanced NASH by combining carbon tetrachloride with high fat & cholesterol diet

NASH is a severe form of NAFLD that can progress to cirrhosis and hepatocellular carcinoma and, its incidence has markedly increased in recent years. Current available animal models fail to reflect the whole spectrum of the disease. We herein designed a Barcelona NASH (BarNa) rat model using the combination of high fat & cholesterol diet with CCl4 inhalation for 10 weeks (NASH) or 24 weeks (NASH-CH). This model reflects the full spectrum of human NASH and present the main characteristics of the disease including: steatosis and metabolic syndrome, lipotoxicity, cellular death, inflammation, hepatic fibrosis and portal hypertension. Moreover, the molecular signature of the BarNa model shared the most important pathways involved in the pathophysiology of the human disease. Overall design: We analyze the whole hepatic transcriptome of wistar rats from three different groups: control, NASH (10 weeks of CCl4+ HF&HCD) or NASH-CH (24 weeks of CCl4+ HF&HCD). N=6 each group.