Pterostilbene improves hepatic lipid accumulation via the miR-34a/Sirt1/SREBP-1 pathway in fructose-fed rats
Pterostilbene improves hepatic lipid accumulation via the miR-34a/Sirt1/SREBP-1 pathway in fructose-fed rats
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紫檀芪通过 miR-34a/Sirt1/SREBP-1 通路改善果糖喂养大鼠的肝脏脂质积累
DOI：
10.1021/acs.jafc.9b04259
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发表时间：
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通讯作者：
Lingdong Kong
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作者：
Wenyuan Wu;Xiaoqin Ding;Tingting Gu;Wenjie Guo;Ruiqing Jiao;Lin Song;Yang Sun;Ying Pan;Lingdong Kong
高果糖摄入促进肝脏脂质积累。紫檀芪是一种天然的白藜芦醇类似物，存在于浆果中，具有保护肝脏的特性。本实验研究了紫檀芪对果糖诱导的肝脏脂质积累的保护作用，并探讨了其可能的机制。我们观察到，在果糖刺激下，大鼠肝脏以及BRL-3A和HepG2细胞中，microRNA-34a （miR-34a，P< 0.05）高表达，而其靶点sirtuin1 （Sirt1, mRNA:P< 0.01；蛋白：P< 0.001）低表达，下游固醇调节元件结合蛋白-1 （SREBP-1）脂肪生成途径（核SREBP-1蛋白：P< 0.05;FASandSCD1mRNA:P< 0.01）过度激活。更有趣的是，紫芪恢复了果糖干扰的miR-34a表达（比果糖对照组0.3 - 0.5倍，P< 0.05）、Sirt1蛋白水平（比果糖对照组1.2- 1.5倍，P< 0.05）和SREBP-1脂质生成途径，导致动物肝细胞脂质积累显著改善[肝甘油三酯和总胆固醇（TG&TC） mg/g·湿组织：4.90±0.19、5.23±0.16、5.20±0.29比果糖对照组9.73±1.06，P< 0.001]；3.18±0.30,3.31±0.39,3.37±0.47 vs 5.67±0.28，P< 0.001]和细胞模型（BRL-3A TG&TC mmol/g·protein: 0.123±0.011 vs 0.177±0.004，P< 0.001; 0.169±0.011 vs 0.202±0.008，P< 0.05; HepG2: 0.257±0.005 vs 0.303±0.016，P< 0.05; 0.143±0.004 vs 0.201±0.008，P< 0.001）。这些结果为紫檀芪通过调节miR-34a/Sirt1/SREBP-1途径抑制果糖诱导的肝脏脂质积累提供了实验证据。
High fructose intake promotes hepatic lipid accumulation. Pterostilbene, a natural analogue of resveratrol found in diet berries, exhibits a hepatoprotective property. Here, we studied the protection by pterostilbene against fructose-induced hepatic lipid accumulation and explored its possible mechanism. We observed a high expression of microRNA-34a (miR-34a,P< 0.05) and a low expression of its target, sirtuin1 (Sirt1, mRNA:P< 0.01; protein:P< 0.001), with the overactivation of downstream sterol regulatory element-binding protein-1 (SREBP-1) lipogenic pathway (nuclear SREBP-1 protein:P< 0.05;FASandSCD1mRNA:P< 0.01), in rat livers, as well as BRL-3A and HepG2 cells, stimulated by fructose. More interestingly, pterostilbene recovered the fructose-disturbed miR-34a expression (0.3–0.5-fold vs fructose control,P< 0.05), Sirt1 protein level (1.2- to 1.5-fold vs fructose control,P< 0.05), and SREBP-1 lipogenic pathway, resulting in significant amelioration of hepatocyte lipid accumulation in animal [hepatic triglyceride and total cholesterol (TG&TC) mg/g·wet tissue: 4.90 ± 0.19, 5.23 ± 0.16, 5.20 ± 0.29 vs fructose control 9.73 ± 1.06,P< 0.001; 3.18 ± 0.30, 3.31 ± 0.39, 3.37 ± 0.47 vs 5.67 ± 0.28,P< 0.001] and cell models (BRL-3A TG&TC mmol/g·protein: 0.123 ± 0.011 vs 0.177 ± 0.004,P< 0.001; 0.169 ± 0.011 vs 0.202 ± 0.008,P< 0.05; HepG2: 0.257 ± 0.005 vs 0.303 ± 0.016,P< 0.05; 0.143 ± 0.004 vs 0.201 ± 0.008,P< 0.001). These results provide the experimental evidence supporting the anti-lipogenic effect of pterostilbene against fructose-induced hepatic lipid accumulation via modulating the miR-34a/Sirt1/SREBP-1 pathway.