Differential expression of liver proteins between obesity-prone and obesity-resistant rats in response to a high-fat diet

摘要

Rodents respond to a chronic high-fat diet (HFD) in two ways: some readily become obese (obesity prone, OP) and others do not (obesitynresistant, OR). Although several hypotheses have been proposed, the mechanisms underlying the inter-individual susceptibility to diet-ninduced obesity remain to be fully defined. In the present study, two-dimensional gel electrophoresis (2-DE) combined with matrix-nassisted laser desorption ionisation time-of-flight MS was carried out for identification of differentially expressed liver proteins in OPnand OR rats fed a HFD, in an attempt to discover marker proteins involved in susceptibility and/or resistance to obesity in rat liver.nThe 2-DE analysis demonstrated that forty spots from 380 visualised spots were differentially regulated between the groups. Amongnthese forty spots, twelve were differentially expressed proteins between OP and OR rats, reaching statistical significance. Of these, fivenproteins have already been linked to obesity; however, seven proteins involved in obesity susceptibility or resistance were identifiednfor the first time in the present study. In order to validate the proteomic results and gain insight into the metabolic changes betweennthe OP and OR groups, we further confirmed the expression pattern of some proteins of interest by Western blot analysis. Combinednresults of proteomic analysis with Western blot analysis revealed that reduced lipogenesis and increased fat oxidation were achieved innthe livers of OR rats. In conclusion, the present proteomic study is an important advance over the previous steps required for identificationnof OP and OR rats, and should prove valuable in the search for the pathogenesis of obesity in humans.