Hepatic proteomic analysis revealed altered metabolic pathways in insulin resistant Akt1+/−/Akt2−/− mice

ObjectiveThe aim of this study was to identify liver proteome changes in a mouse model of severe insulin resistance and markedly decreased leptin levels.MethodsTwo-dimensional differential gel electrophoresis was utilized to identify liver proteome changes in AKT1+/−/AKT2−/− mice. Proteins with altered levels were identified with tandem mass spectrometry. Ingenuity Pathway Analysis was performed for the interpretation of the biological significance of the observed proteomic changes.Results11 proteins were identified from 2 biological replicates to be differentially expressed by a ratio of at least 1.3 between age-matched insulin resistant (Akt1+/−/Akt2−/−) and wild type mice. Albumin and mitochondrial ornithine aminotransferase were detected from multiple spots, which suggest post-translational modifications. Enzymes of the urea cycle were common members of top regulated pathways.ConclusionOur results help to unveil the regulation of the liver proteome underlying altered metabolism in an animal model of severe insulin resistance.