| Experiment Id | GSE75475 | Name | Circadian Homeostasis of Liver Metabolism Suppresses Hepatocarcinogenesis |
| Experiment Type | transcription profiling by array | Study Type | Baseline |
| Source | GEO | Curation Date | 2022-03-15 |
| description | Chronic jet lag induces spontaneous hepatocellular carcinoma (HCC) in wild-type mice following a pathophysiological pathway very similar to that observed in obese humans. This process initiates with non-alcoholic fatty liver disease (NAFLD), progresses to steatohepatitis and fibrosis before HCC detection, and is driven by persistent genome-wide gene deregulation that induces global liver metabolic dysfunction. Nuclear receptor-controlled cholesterol/bile acid and xenobiotic metabolism are found among top deregulated pathways. Ablation of the bile acid receptor FXR dramatically increases intrahepatic bile acid levels and jet-lag-induced HCC, while loss of CAR, a well-known liver tumor promoter, inhibits NAFLD-induced hepatocarcinogenesis. Circadian disruption activates CAR by promoting cholestasis, peripheral clock disruption, and sympathetic dysfunction. Thus, FXR and CAR are clock-controlled therapeutic targets for spontaneous HCC Male C57BL/6 inbred Wild-type (WT) mice were single-housed and kept either in steady 12hr light/12hr dark cycles (NS) or subjected to chronic jet-lag (CJ) from 4 weeks of age between two time zones different at the time of light onset for 8 hours. Total liver RNA was isolated from control (NS) and jet-lagged (CJ) mice of 12 and 30 weeks of age at ZT2, 10 and 18 (ZT: Zeitgeber time with light on at ZT0 and off at ZT12), snap-frozen, and used for an Agilent array. Data obtained was analyzed using the Limma Bioconductor package after normalization and batch effect removal. |
