Hepatic Gene Expression And Proteomic Profile Of Mice With Nonalcoholic Fatty Liver Disease Due To High Fat Diet

Introduction Although nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, the responsible molecular mechanisms are incompletely understood. Here, we performed hepatic gene expression and proteomic analysis in mice with NAFLD due to a high saturated fat diet. Materials and Methods: Male C57/BL6 mice were fed 60% lard or control diet for 8 weeks. Those on the high fat diet developed hepatic steatosis. Hepatic gene expression was analyzed by microarray technology, and the proteome was analyzed by two‐dimensional difference gel electrophoresis with mass spectrometry. Results Compared to control diet, high fat diet changed the expression of 473 genes (256 up‐ and 217 down‐regulated) by 2‐fold or greater. Multiple genes encoding proteins involved in fatty acid oxidation were up‐regulated. Several genes encoding extracellular matrix proteins, adhesion molecules, and xenobiotic metabolizing enzymes were down‐regulated. Proteomic analysis revealed eleven proteins which were differentially expressed. Of these, glutathione S‐transferase mu1 and pi, and selenium binding protein 2 were decreased on both gene chip and proteomic analysis. Conclusion NAFLD due to a high saturated fat diet in mice is associated with specific gene expression and proteomic changes. This work was supported by the NIH (IVD, CJM), the AASLD (MC) and the VA (CJM).