Transcriptome analysis revealed association of some P450 genes with obesity in a polygenic obese mouse model

Superfamily of cytochromes P450 (CYP) have been extensively investigated in xenobiotic metabolism studies but only a handful of these genes (e.g., Cyp19a1 and Cyp7a1) have been associated with obesity. Examining these associations in animal models is relevant since obesity and metabolic syndrome in humans have become a prevalent health problem. In previous studies we identified four loci affecting obesity in mouse lines selected for high (Fat line) or low (Lean line) body fat content. Here we developed a Congenic line carrying a chromosome 15 obesity segment from the Lean line and compared its liver transcriptome and obesity traits with the original Fat line. Congenic segment exhibited therapeutic effect on several obesity-related parameters such as lowering fat depot size by up to 29% and lowering fasting glucose levels. Using the Steroltalk microarray focused on cytochromes P450 and cholesterol metabolism, we identified 9 differentially expressed genes including two Cyp genes (Cyp26a1, Cyp2a4). Given the scarcity of literature reporting associations between obesity and Cyps, our results suggest that these genes might play a more pronounced role in regulating obesity than previously thought. Further functional studies are needed to explain the mechanism by which perturbations in these Cyps affect obesity in our polygenic model.