Avtor/Urednik     Simončič, Matjaž; Režen, Tadeja; Juvan, Peter; Fievet, Catherine; Staels, Bart; Rozman, Damjana; Horvat, Simon
Naslov     Transcriptome analysis revealed association of some P450 genes with obesity in a polygenic obese mouse model
Tip     članek
Vir     Acta Chim Slov
Vol. in št.     Letnik 55, št. 1
Leto izdaje     2008
Obseg     str. 101-10
Jezik     eng
Abstrakt     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.
Deskriptorji     OBESITY
CYTOCHROME P-450
CHOLESTEROL
GENE EXPRESSION
DISEASE MODELS, ANIMAL
MICE