Many genes are constitutively activated by PPARα, a protein that is enhanced by mobilization of fatty acids during fasting. Here, analyses of livers from mice fed ad libitum demonstrate an extensive suppression of this constitutive PPAR regulation with Cyp1b1 deletion. Much of this suppression process diverts hepatic fatty acid metabolism from the formation of triglyceride droplets to mitochondrial oxidation and glycogen storage. Substantial differences in gene expression in Cyp1b1-ko mice fed high or low fat diets suggests that Cyp1b1 metabolism of endogenous substrates affects extra-hepatic signaling to the hepatocyte, thereby controlling fatty acid metabolism within these cells. Adipose suppression is similar in male and female mice, yet many gene changes suggest affects on sexually dimorphic control. Estradiol is a Cyp1b1 substrate [20], which is generated by aromatase within the hypothalamus and controls energy homeostasis through activation of estrogen receptor alpha (ER-α) [21–22]. One possibility is that increased estradiol concentrations in the hypothalamus may affect sexually dimorphic responses in Cyp1b1-ko mice.
