We found that IMP significantly enhanced SIRT1 and FXR expression in APAP overdose-induced WT mice while the activation of expression of FXR with IMP or OCA treatment was partially lost in SIRT1−/− PMHs, indicating that SIRT1-AMPK activation contributes to the IMP-mediated FXR signaling against APAP overdose-induced liver injury. This evidence concerns the gene NR1H4 and injury.