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 therapeutic 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 supplemented 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 subsequently 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 higher 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 models 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.The authors received funding from the Health Department of the Regional Government of Andalucía (Consejería de Salud de la Junta de Andalucía), project number PC-0148- 2016-0148 awarded to Dr. Francisco Martín Bermudo and Dr. Rocío Gallego-Durán; Instituto de Salud Carlos III, project number PI16/01842 awarded to Dr. Manuel Romero Gómez and Dr. Javier Ampuero Herrojo; and Health Department of the Regional Government of Andalucía , project number PAI-BIO311 awarded to Dr. Francisco Martín Bermudo