High-throughput sequencing reveals induction of drug metabolism in various cholestatic livers

Cholestasis is a multifactorial disorder that compromises liver function. We wanted to examine Phase I and II drug metabolism in cholestatic livers. We performed high-throughput sequencing on livers from Fxr-/- Shp-/- double knockout mice, which mimic juvenile cholestasis. Next, we used comparative transcriptomic approach to test if the induction in drug metabolism is also seen in models of liver injury, including steatosis, regeneration and bile acid-stressed livers. Hepatic mRNA expression profiles of adult wild type, CAR-activated (TCPOBOP injected) (n=2), Fxr-/- Shp-/- (n=3), high fat diet-fed (n=2), partial hepatectomized (n=3) and bile acid diet-fed (n=3) mice.