| First Author | Kettner NM | Year | 2016 |
| Journal | Cancer Cell | Volume | 30 |
| Issue | 6 | Pages | 909-924 |
| PubMed ID | 27889186 | Mgi Jnum | J:237981 |
| Mgi Id | MGI:5817823 | Doi | 10.1016/j.ccell.2016.10.007 |
| Citation | Kettner NM, et al. (2016) Circadian Homeostasis of Liver Metabolism Suppresses Hepatocarcinogenesis. Cancer Cell 30(6):909-924 |
| abstractText | Chronic jet lag induces spontaneous hepatocellular carcinoma (HCC) in wild-type mice following a mechanism very similar to that observed in obese humans. The process initiates with non-alcoholic fatty liver disease (NAFLD) that progresses to steatohepatitis and fibrosis before HCC detection. This pathophysiological pathway is driven by jet-lag-induced genome-wide gene deregulation and global liver metabolic dysfunction, with nuclear receptor-controlled cholesterol/bile acid and xenobiotic metabolism among the top deregulated pathways. Ablation of farnesoid X receptor dramatically increases enterohepatic bile acid levels and jet-lag-induced HCC, while loss of constitutive androstane receptor (CAR), a well-known liver tumor promoter that mediates toxic bile acid signaling, inhibits NAFLD-induced hepatocarcinogenesis. Circadian disruption activates CAR by promoting cholestasis, peripheral clock disruption, and sympathetic dysfunction. |
