胆固醇酯对非酒精性脂肪肝药物治疗的影响

Effect of Cholesteryl Ester on Drug Treatment in Non-Alcoholic Fatty Liver Disease

摘要:

胆固醇酯(cholesteryl ester，CE)是胆固醇过量时的储存产物。研究表明CE在多种代谢类疾病的诊疗中都扮演着重要角色，然而膳食摄入CE对非酒精性脂肪肝(non-alcoholic fatty liver disease, NAFLD)药物治疗的影响仍不清晰。作者以非诺贝特(fenofibrate, Feno)治疗的NAFLD小鼠为模型，通过膳食补充CE研究其对非诺贝特治疗效果的影响。结果表明，非诺贝特可有效缓解NAFLD的症状，而膳食补充CE后削弱了非诺贝特对NAFLD的治疗效果。此外，转录组学以及RT-QPCR分析表明，膳食补充CE可逆转非诺贝特调控的脂肪酸代谢以及胆固醇酯化相关基因 Soat1 和 Soat2 mRNA的表达。以上结果表明，膳食添加CE可显著影响NAFLD的药物治疗效果，推测当饮食中CE质量分数较高时，非诺贝特的治疗效果将被降低。该研究为非酒精性脂肪肝患者接受药物治疗期间的合理膳食提供了理论依据。

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.