Activation of AMPK bymetformin, a commonly used drug for the treatment of type 2 diabetes, leads to theinhibition of FXR transcriptional activity by impairing coactivator binding.Reduced FXR target gene expression by metformin-activated AMPK decreases fecalbile acid excretion in wild-type mice, and it aggravates liver injury in an animalmodel of intrahepatic cholestasis (43). The gene discussed is NR1H4; the disease is intrahepatic cholestasis.