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Chunk #20 — RESULTS — Cyp1b1 deletion suppresses post-weaning weight gain

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Cytochrome P450 1B1: An unexpected modulator of liver fatty acid homeostasis.
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The association of Cyp1b1 with adipogenesis and pro-oxidant signaling suggested that Cyp1b1 metabolism may play a significant role in mediating the responsiveness of liver and adipose tissue to dietary fat. Cyp1b1 is appreciably expressed in adipose tissue of C57BL/6j mice, but is expressed at very low levels in the liver [Figure S1B], most of which can be accounted for by expression in endothelial cells (Sheibani et al, unpublished data). To examine this further, we compared the effects of a high fat/low carbohydrate (60 percent fat/20 percent carbohydrate, HFD) and a low fat/high carbohydrate (10 percent fat/70% carbohydrate, LFD) diet on WT and Cyp1b1-ko mice. The two defined diets, which are free of protein-associated isoflavones, are of similar caloric content and are commonly used for studies of DIO [29]. Male and female mice were placed on the respective diet at weaning (postnatal day 21; continued for 6, 11 or 36 weeks) or late in liver maturation (6 weeks of age; 6 week exposure) (Figure 1A). The three periods of HFD intake correspond to different stages of non-alcoholic hepatic steatosis (NASH) in C57BL/6 mice [30].