Molecular and Cellular Biochemistry

, Volume 343, Issue 1–2, pp 59–66 | Cite as

Differential response of two models of genetically modified mice fed with high fat and cholesterol diets: relationship to the study of non-alcoholic steatohepatitis

  • Fernando Rodríguez-Sanabria
  • Anna Rull
  • Gerard Aragonès
  • Raúl Beltrán-Debón
  • Carlos Alonso-Villaverde
  • Jordi Camps
  • Jorge Joven


Research on the molecular basis of the hepatic alterations associated to obesity is dependent on the availability of suitable animal models. Apolipoprotein E deficient mice (ApoE−/−) and LDL-receptor deficient mice (LDLr−/−) develop steatosis and steatohepatitis when given pro-atherogenic diets. However, previous data suggest that these two models are not completely interchangeable, and that their metabolic phenotype may partially differ in response to nutrient stimuli. The present study further investigates this question, by comparing changes in hepatic inflammation, lipoprotein metabolism, and their related gene expressions. LDLr−/− mice were more susceptible to the development of obesity and hepatic steatosis, while the ApoE−/− model increased the amount of macrophages and inflammatory nodules in the liver. These changes were accompanied by a differential expression of selected members of the MAPK family and PPARs in the liver.


Inflammation Non-alcoholic fatty liver disease Non-alcoholic steatohepatitis Steatosis 



This work was supported by grants PI05/1606 and PI08/1381 from the Instituto de Salud Carlos III, Madrid, Spain. Anna Rull is the recipient of a fellowship from the Generalitat de Catalunya (FI-G 0503).

Conflict of interest statement

The authors have declared no conflict of interest.


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Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Fernando Rodríguez-Sanabria
    • 1
  • Anna Rull
    • 1
  • Gerard Aragonès
    • 1
  • Raúl Beltrán-Debón
    • 1
  • Carlos Alonso-Villaverde
    • 1
  • Jordi Camps
    • 1
  • Jorge Joven
    • 1
  1. 1.Centre de Recerca BiomèdicaHospital Universitari Sant Joan de Reus, Institut d’Investigació Sanitària Pere Virgili, Universitat Rovira i VirgiliReusSpain

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