A Mouse Model of Non-Alcoholic Steatohepatitis and Hepatocellular Carcinoma Induced by Western Diet and Carbon Tetrachloride.

Abstract

Non-alcoholic steatohepatitis (NASH) is a severe form of non-alcoholic fatty liver disease (NAFLD). Obesity is a known risk factor of NASH, which, in turn, increases the risk of developing cirrhosis (liver scarring) and hepatocellular carcinoma (HCC). In addition to being a potentially life-threatening condition, public health concerns surrounding NASH are amplified by the lack of FDA-approved treatments. Although various preclinical models reflecting both the histopathology and the pathophysiological progression of human NASH exist, most of these models are diet-based and require 6-13 months for NASH symptom manifestation. Here, we describe a simple and rapid-progression model of NASH and NASH-driven HCC in mice. Mice received a western diet equivalent (WD; i.e., a high-fat, high-fructose, and high-cholesterol diet), high-sugar water (23.1 g/L fructose and 18.9 g/L glucose), and weekly intraperitoneal injections of carbon tetrachloride (CCl4) at a dose of 0.2 μL/g of body weight. The resulting phenotype, consisting in liver fibrosis and HCC, appeared within 24 weeks of diet/treatment initiation and presented similar histological and transcriptomic features as human NASH and NASH-driven HCC, thereby supporting the adequacy of this preclinical model for the development and evaluation of drugs that can prevent or reverse these diseases.

• Authors: Sijing Li, Omar Motiño, Flavia Lambertucci, Hui Chen, Gerasimos Anagnostopoulos, Léa Montégut, Uxía Nogueira-Recalde, Maria Chiara Maiuri, Guido Kroemer, Isabelle Martins
• Journal: Methods in molecular biology (Clifton, N.J.) (Methods Mol Biol) Vol. 2769 Pg. 57-65 ( 2024) ISSN: 1940-6029 [Electronic] United States
• PMID: 38315388 (Publication Type: Journal Article)
• Copyright: © 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.

Chemical References

• Carbon Tetrachloride
• Fructose

Topics

• Humans
• Mice
• Animals
• Non-alcoholic Fatty Liver Disease (etiology, pathology)
• Carcinoma, Hepatocellular (genetics)
• Carbon Tetrachloride (toxicity)
• Liver Neoplasms (pathology)
• Diet, Western (adverse effects)
• Disease Models, Animal
• Liver Cirrhosis (pathology)
• Fructose
• Diet, High-Fat (adverse effects)
• Liver (pathology)
• Mice, Inbred C57BL