| First Author | Bushkofsky JR | Year | 2016 |
| Journal | Arch Biochem Biophys | Volume | 597 |
| Pages | 30-47 | PubMed ID | 27036855 |
| Mgi Jnum | J:248903 | Mgi Id | MGI:6092594 |
| Doi | 10.1016/j.abb.2016.03.030 | Citation | Bushkofsky JR, et al. (2016) Cyp1b1 affects external control of mouse hepatocytes, fatty acid homeostasis and signaling involving HNF4alpha and PPARalpha. Arch Biochem Biophys 597:30-47 |
| abstractText | Cytochrome P450 1b1 (Cyp1b1) is expressed in endothelia, stellate cells and pre-adipocytes, but not hepatocytes. Deletion alters liver fatty acid metabolism and prevents obesity and hepatic steatosis. This suggests a novel extra-hepatocyte regulation directed from cells that express Cyp1b1. To characterize these mechanisms, microarray gene expression was analyzed in livers of normal and congenic Cyp1b1-ko C57BL/6 J mice fed either low or high fat diets. Cyp1b1-ko gene responses indicate suppression of endogenous PPARalpha activity, a switch from triglyceride storage to mitochondrial fatty acid oxidation and decreased oxidative stress. Many gene responses in Cyp1b1-ko are sexually dimorphic and correspond to increased activity of growth hormone mediated by HNF4alpha. Male responses stimulated by GH pulses are enhanced, whereas responses that decline exhibit further suppression, including Cyp regulation by PPARalpha, CAR and PXR. These effects of Cyp1b1 deletion overlap with effects caused by deletion of the small heterodimeric partner, a suppressor of these nuclear factors. Redirection of gene expression associated with liver fat homeostasis in Cyp1b1-ko mice that directs hypothalamic control of GH and leptin. Cyp1b1-ko suppresses neonatal Scd1 and delays adult maturation of dimorphic GH/HNF4alpha signaling. Alternatively, deletion may diminish hypothalamic metabolism of estradiol, which establishes adult GH regulation. |
