BackgroundThe nuclear receptor corepressor 1 (NCOR1) plays an important role in the regulation of gene expression in immunometabolic conditions by connecting chromatin-modifying enzymes, coregulators and transcription factors. NCOR1 has been shown to be involved in cardiometabolic diseases. Recently, we demonstrated that the deletion of macrophage NCOR1 aggravates atherosclerosis by promoting CD36-triggered foam cell formation via PPARG derepression.PurposeSince NCOR1 modulates the function of several key regulators involved in hepatic lipid and bile acid metabolism, we hypothesized that its deletion in hepatocytes alters lipid metabolism and atherogenesis.MethodsTo test this hypothesis, we generated hepatocyte-specificNcor1knockout mice on aLdlr-/- background. Besides assessing the progression of the disease in thoracoabdominal aortaeen face, we analyzed hepatic cholesterol and bile acid metabolism at expression and functional levels.ResultsOur data demonstrate that liver-specificNcor1knockout mice on an atherosclerosis-prone background develop less atherosclerotic lesions than controls. Interestingly, under chow diet, plasma cholesterol levels of liver-specificNcor1knockout mice were slightly higher compared to control, but strongly reduced compared to control mice after feeding them an atherogenic diet for 12 weeks. Moreover, the hepatic cholesterol content was decreased in liver-specificNcor1knockout compared to control mice. Our mechanistic data revealed that NCOR1 reprograms the synthesis of bile acids towards the alternative pathway, which in turn reduce bile hydrophobicity and enhances fecal cholesterol excretion.ConclusionsOur data suggest that hepaticNcor1deletion in mice decreases atherosclerosis development by reprograming bile acid metabolism and enhancing fecal cholesterol excretion.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12933-023-01865-w.