Cyp1b1 expression increases in the early phase of in vitro adipogenic differentiation, in parallel with PPARγ expression [5]. The endothelium plays a critical role in the development and maintenance of both liver and adipose tissue. Cyp1b1 expression in endothelial cells and pericytes decreases peroxidation of unsaturated fatty acids, while promoting capillary morphogenesis in vitro, and neovascularization in vivo [8–9, 18–19]. The association of Cyp1b1 activity with adipogenic PPARγ expression and decreased fatty acid peroxidation suggests that Cyp1b1 may play an important role in this aspect of energy homeostasis. To test this hypothesis, we maintained C57BL/6j (WT) and Cyp1b1-null (Cyp1b1-ko) mice on either a low fat/high carbohydrate diet (LFD) or a near iso-caloric high fat/low carbohydrate diet (HFD). We used various time periods post-weaning, which distinguish different phases of the response to high dietary fat. We report that Cyp1b1 deletion lowers adiposity without affecting caloric intake, suggesting altered energy utilization.