NR1H4 and metabolic dysfunction-associated steatohepatitis: Hepatocytes under significant cellular stress may be vulnerable to apoptosis, especially under hepatic conditions such as NAFLD or NASH.194 FXR plays a significant hepatoprotective role against apoptosis in which non-ligand-bound FXR binds to the death effector domain of caspase-8, inhibiting extrinsic apoptosis (Fig. 11b).195 FXR additionally prevents apoptosis by inducing Cytochrome P450 Family 4 Subfamily F (CYP4F)-mediated metabolism of pro-apoptotic deoxysphingolipids and by preventing BA-induced apoptosis by repressing CYP7A1/CYP8B1 expression.196–198