Endocrine Abstracts

Background: The variablity of the individual susceptibility to diet-induced obesity and insulin resistance is well known, but so far insufficiently explained. As skeletal muscle metabolism and insulin sensitivity are important pathophysiologic features of obesity-asscociated metabolic perturbations, we tried to identify differences in muscular gene expression profiles between high fat fed rats prone to develop obesity (diet-induced obesity, DIO) and those which remained lean (diet-resistant, DR).

Methods: Wistar-Rats were fed ad libitum with a high fat diet (HF, 40 energy% of fat) for 12 weeks. Weight changes and food intake as well as serum and cerebral spinal fluid (CSF) glucose, insulin, leptin and adiponectin were monitored during the diet phase. Using these parameters, a model for the identification of DIO rats was established. Next, gene expression profiles were obtained using Affymetrix GeneChips from the M. gastrocnemius of DIO and DR rats after one week of HF diet, i.e. before induction of obesity.

Results: No clear association between the animals’ weight curves and any serum or CSF parameter was noticed, whereas the ratio between the absolute weight gain after one week and the rats’ initial weight (weight gain index, WGI) was significantly correlated with the final weight and could therefore be used to predict obesity susceptibility. In skeletal muscle of DIO rats we detetected a striking transcriptional upregulation of genes from the MAP (mitogen acivated protein)-kinase pathway, intracellular calcium-sensing, pyruvate metabolism and of Rab-asscociated proteins participating in vesicle transport and GLUT4 translocation.

Conclusion: The prediction of susceptibility to diet-induced obesity is possible using simple auxologic parameters. Individual differences in skeletal muscle gene expression could contribute to the development of the DIO/DR-phenotype.