NR1H4 and fatty liver disease: A preclinical study by Ma et al. reported that the knockout mouse model for Fxr gene (Fxr−/− mice) spontaneously developed hepatic steatosis with elevated levels of FFAs and insulin resistance [59], whereas Kunne et al. studied mice with the depletion of hepatic cytochrome P450 reductase (Hrn mice), demonstrating that Hrn animals developed fatty liver due to the absence of bile acid synthesis [60].