Silybin ameliorates hepatic lipid accumulation and modulates global metabolism in an NAFLD mouse model
Silybin ameliorates hepatic lipid accumulation and modulates global metabolism in an NAFLD mouse model
复制标题
水飞蓟宾改善 NAFLD 小鼠模型中的肝脏脂质积累并调节整体代谢
DOI：
10.1016/j.biopha.2019.109721
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发表时间：
2020-03-01
影响因子：
7.5
通讯作者：
Xie, Yuan
中科院分区：
文献类型：
--
作者：
Sun, Runbin;Xu, Dan;Xie, Yuan
水飞蓟宾具有良好的抗肥胖和代谢综合征作用，但水飞蓟宾的全身调节作用尚未完全显现。本研究旨在探讨水飞蓟宾对非酒精性脂肪性肝病(NAFLD)的代谢调节作用。C57BL/6J小鼠喂饲高脂/高胆固醇饲料8周，最后4周灌胃给予水飞蓟宾(50或100 mg/kg/d)和牛磺熊脱氧胆酸钠(TUDCA，50 mg/kg/d)。通过血液生化指标、肝脂测定和肝脏油红O染色，评价水飞蓟宾和TUDCA的降脂作用。采用基于气相色谱-质谱仪(GC/MS)的代谢组学平台检测血清和肝脏样品。多变量/单变量数据分析和通径分析用于研究差异代谢物和代谢途径。结果表明，小鼠NAFLD模型建立成功，水飞蓟宾和TUDCA均能显著降低血清和肝脏脂质蓄积。血清和肝脏的代谢组学分析表明，高脂/高胆固醇饮食导致脂肪代谢、多元醇代谢、氨基酸代谢、尿素循环和TCA循环等代谢物代谢异常。水飞蓟宾和TUDCA治疗均可逆转HFD喂养引起的代谢紊乱。综上所述，高脂/高胆固醇饮食导致小鼠血清和肝脏代谢异常，水飞蓟宾治疗改善了肝脏脂质蓄积，调节了全球代谢途径，为其多靶点机制提供了可能的解释。
Silybin shows good effects against obesity and metabolic syndrome, but the systemic modulation effect of silybin has not been fully revealed. This study aims to investigate the metabolic regulation by silybin of nonalcoholic fatty liver disease (NAFLD). C57BL/6 J mice were fed a high-fat/high-cholesterol diet for 8 weeks and treated with silybin (50 or 100 mg/kg/day) and sodium tauroursodeoxycholate (TUDCA, 50 mg/kg/day) by gavage for the last 4 weeks. Blood biochemical indexes and hepatic lipid measurement as well as Oil red O staining of the liver were conducted to evaluate the model and the lipid-lowering effect of silybin and TUDCA. Furthermore, serum and liver samples were detected by a metabolomic platform based on gas chromatography-mass spectrometry (GC/MS). Multivariate/univariate data analysis and pathway analysis were used to investigate differential metabolites and metabolic pathways. The results showed that the mouse NAFLD model was established successfully and that silybin and TUDCA significantly lowered both serum and hepatic lipid accumulation. Metabolomic analysis of serum and liver showed that a high-fat/high-cholesterol diet caused abnormal metabolism of metabolites involved in lipid metabolism, polyol metabolism, amino acid metabolism, the urea cycle and the TCA cycle. Silybin and TUDCA treatment both reversed metabolic disorders caused by HFD feeding. In conclusion, a high-fat/high-cholesterol diet caused metabolic abnormalities in the serum and liver of mice, and silybin treatment improved hepatic lipid accumulation and modulated global metabolic pathways, which provided a possible explanation of its multiple target mechanism.