The lipogenic genes Scd1, Pdk4, Elovl5 and Me1 are suppressed in both male 11 week and female 36 week Cyp1b1-ko mice on the HFD. Scd1 suppression increases fatty acid oxidation, while decreasing storage as triglycerides in lipid droplets. This lipogenic gene expression is directed by Srebp-1c, which is inhibited by AMP-activated protein kinase (AMPK) [81–82]. AMPK is activated in hepatocytes, in vivo, by leptin activity, which is directed from the VMH via the sympathetic nervous system (Figure 9). Leptin also similarly stimulates lipolysis in the fat pad [21, 83–85]. An enhanced uptake of leptin into the VMH in Cyp1b1-ko mice is supported by acceleration of the normal fasting-induced decline of serum leptin [21] (Figure 4B). This uptake may be enhanced if the blood brain barrier is indeed altered by effects of Cyp1b1 deletion on pericyte-endothelial coupling. Leptin participation is also supported by the continued obesity of leptin-deficient Cyp1b1-ko mice (Figure 4E).
