Abstract:Cholesteryl ester (CE) is a storage product of excessive cholesterol. Studies have shown that CE plays an important role in the diagnosis and treatment of various metabolic diseases, but the effect of dietary CE on drug treatment for non-alcoholic fatty liver disease (NAFLD) is still unclear. Using a NAFLD mouse model treated with fenofibrate (Feno), the effect of dietary CE supplementation on the efficacy of Fenotreatment was investigated. Results showed that Feno effectively alleviated NAFLD symptoms, but dietary CE supplementation weakened its therapeutic effect. Furthermore, transcriptomics analysis and RT-QPCR showed that dietary CE could reverse the expression of fatty acid metabolism and cholesterol esterification related genes, i.e., Soat1 and Soat2 mRNA, regulated by Feno. These results suggest that dietary CE intake significantly impacts the drug treatment for NAFLD, and it is speculated that the higher intake of CE may reduce the efficacy of Feno treatment. This study provides a theoretical basis for the reasonable diet for patients with NAFLD during drug treatment.