Long-term exposure to hypercaloric high fat diet induced marked tissue fatty acid accumulation and may influence cell function. Previous results in our laboratory showed that uncoupling proteins (UCPs) and fatty acid-binding protein (FABP) gene expression are changed in adipose tissue and skeletal muscle tissue in diet-induced (cafeteria) obese animals. The aim of this study was to examine heart FABP (HFABP) and UCP2 gene expressions in dietary obese rats. Rats fed on a high-fat diet for 65 days had significantly higher fat stores and body weight than control rats. Interestingly, we found that both HFABP and UCP2 mRNA levels were significantly reduced in cafeteria-obese rats when compared to control animals. Moreover, a statistically significant correlation was observed between the two gene expression levels. The down-regulation of heart HFABP and UCP2 parallels the lower lipid utilization which may account for an enhanced fat deposition. It is plausible that these two genes are regulated by the same family of transcription factors.