| First Author | Larsen MC | Year | 2015 |
| Journal | Arch Biochem Biophys | Volume | 571 |
| Pages | 21-39 | PubMed ID | 25703193 |
| Mgi Jnum | J:230258 | Mgi Id | MGI:5755894 |
| Doi | 10.1016/j.abb.2015.02.010 | Citation | Larsen MC, et al. (2015) Cytochrome P450 1B1: An unexpected modulator of liver fatty acid homeostasis. Arch Biochem Biophys 571:21-39 |
| abstractText | Cytochrome P450 1b1 (Cyp1b1) expression is absent in mouse hepatocytes, but present in liver endothelia and activated stellate cells. Increased expression during adipogenesis suggests a role of Cyp1b1 metabolism in fatty acid homeostasis. Wild-type C57BL/6j (WT) and Cyp1b1-null (Cyp1b1-ko) mice were provided low or high fat diets (LFD and HFD, respectively). Cyp1b1-deletion suppressed HFD-induced obesity, improved glucose tolerance and prevented liver steatosis. Suppression of lipid droplets in sinusoidal hepatocytes, concomitant with enhanced glycogen granules, was a consistent feature of Cyp1b1-ko mice. Cyp1b1 deletion altered the in vivo expression of 560 liver genes, including suppression of PPARgamma, stearoyl CoA desaturase 1 (Scd1) and many genes stimulated by PPARalpha, each consistent with this switch in energy storage mechanism. Ligand activation of PPARalpha in Cyp1b1-ko mice by WY-14643 was, nevertheless, effective. Seventeen gene changes in Cyp1b1-ko mice correspond to mouse transgenic expression that attenuated diet-induced diabetes. The absence of Cyp1b1 in mouse hepatocytes indicates participation in energy homeostasis through extra-hepatocyte signaling. Extensive sexual dimorphism in hepatic gene expression suggests a developmental impact of estrogen metabolism by Cyp1b1. Suppression of Scd1 and increased leptin turnover support enhanced leptin participation from the hypothalamus. Cyp1b1-mediated effects on vascular cells may underlie these changes. |
