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

Rev Esp Enferm Dig. 2019 Apr;111(4):301-307. doi: 10.17235/reed.2019.6083/2018.

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 had 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 aided in the selection of a long-term, more physiological model for physiopathology studies or a more rapid NASH model for novel molecule testing.

MeSH terms

  • Alanine Transaminase / blood
  • Animals
  • Aspartate Aminotransferases / blood
  • Body Weight
  • Cholesterol / blood
  • Choline*
  • Diet, High-Fat*
  • Disease Models, Animal*
  • Fructose / administration & dosage*
  • Liver / enzymology
  • Liver / pathology
  • Male
  • Methionine / administration & dosage*
  • Mice
  • Mice, Inbred C57BL
  • Non-alcoholic Fatty Liver Disease / blood
  • Non-alcoholic Fatty Liver Disease / etiology*
  • Non-alcoholic Fatty Liver Disease / pathology
  • Random Allocation
  • Sweetening Agents / administration & dosage*

Substances

  • Sweetening Agents
  • Fructose
  • Cholesterol
  • Methionine
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Choline