Metabolic characterization of two different non-alcoholic fatty liver disease pre-clinical mouse models

Abstract

Introduction: non-alcoholic fatty liver disease is one of the most prevalent liver disorders in the developed world. Currently, there is no approved pharmacological therapy except for lifestyle intervention. Therefore, there is a need to increase the knowledge of preclinical models in order to boost novel discoveries that could lead to a better thera peutic management. Material and methods: this study characterized the effects of two different diets, a long-term high-fat high-fructose diet (HF-HFD) and a choline-deficient, methionine supple mented high-fat diet (CDA-HFD) in C57BL/6J mice for 52 weeks or 16 weeks, respectively. Body weight, lipid and hepatic profile were analyzed and liver histology was sub sequently evaluated. Results: HF-HFD animals showed an increased body weight and total cholesterol levels, whereas the opposite occurred in CDA-HFD. Both HF-HFD and CDA-HFD animals had high er ALT and AST levels. With regard to histology findings, HF-HFD and CDA-HFD diets induced an increased collagen deposit and intrahepatic steatosis accumulation. Conclusion: in conclusion, the comparison of these mod els helped us to decide if it is better to select a long-term but more physiological model for physiopathology studies or either a more rapid NASH model for novel molecules testing.