Data in this study indicate that HNF4α antagonizes the transactivation of SREBP-1C by LXR to control hepatic lipid metabolism, and thus establishes partial deficiency of HNF4α as a key mechanism of the dysregulation of the two master lipogenic factors LXR and SREBP-1C during hepatosteatosis and hyperlipidemia. The gene discussed is SREBF1; the disease is hyperlipidemia.