Seven neutered/spayed obese beagles (> 35% body fat; average age = 5.86 ± 3.34 years; average weight = 17.0 ± 3.7 kg) were identified for a weight loss study to test the efficacy of a dry low-fat, fiber-enhanced therapeutic food formulated for weight loss (33.2% crude protein, 8.7% crude fat and 26.7% total dietary fiber on dry matter basis). The dogs were fed for weight loss (1.0 X RER) for a period of 4 months. During the study all dogs underwent DEXA and chemistry screen analysis at 0, 1, 2, 3 and 4 months. In addition, blood samples were collected into PAXgene blood RNA tubes at the beginning and end of the study to characterize changes in gene expression differences resulting from weight loss on the food. RNA was extracted according to the procedures provided in the PAXgene Blood RNA Kit Handbook (Qiagen, Valencia, CA). RNA was hybridized to an Affymetrix Gene Chip Canine-2 Genome Array and signal normalized using Robust Multi-Array Average. Data was filtered using following a false discovery rate of 0.1 and > 1.3-fold change were considered different for day 0 and end of study. On average, dogs lost 2.8 ± 0.8 kg body fat (41.2% of initial fat mass) in 4 months. Gene expression profiles were modified in these dogs after 4 months of weight loss on the food. The nutrigenomic effect of the food can be seen in the shift from an obese to a lean profile. Of the genes identified, there was a down regulation of genes associated with fat accumulation including: long chain fatty acid CoA ligase 1, growth factor receptor-bound protein 2 and hypoxia-inducible factor 1 alpha. In summary, obese dogs fed the weight loss food lost 2.8 ± 0.8 kg (41.2% of initial fat mass) body fat in 4 months which was accompanied by a shift from an obese to lean genomic profile.