Resveratrol improves non-alcoholic fatty liver disease by activating AMP-activated protein kinase
Resveratrol improves non-alcoholic fatty liver disease by activating AMP-activated protein kinase
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DOI：
10.1111/j.1745-7254.2008.00807.x
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发表时间：
2008-06-01
影响因子：
8.2
通讯作者：
Xiao, Hu
中科院分区：
文献类型：
--
作者：
Shang, Jing;Chen, Lu-lu;Xiao, Hu
目的：探讨白藜芦醇（resveratrol， RSV）对非酒精性脂肪性肝病（NAFLD）的治疗作用及其可能机制。方法：采用高脂饲料饲养的大鼠感染RSV。观察肝脏组织学。采用高胰岛素正糖钳夹法评估胰岛素敏感性。在HepG2细胞中诱导脂肪堆积，并用RSV处理细胞。在动物研究和细胞研究中测定了amp活化蛋白激酶（AMPK）的磷酸化水平。结果：高脂饮食大鼠出现腹部肥胖、NAFLD和胰岛素抵抗（IR）， RSV给药10周后明显改善。RSV处理阻止了高浓度葡萄糖和胰岛素培养的HepG2细胞中甘油三酯（TG）的积累。体内和体外研究均表明，RSV处理可促进AMPK的磷酸化，在本研究中，AMPK可抑制2个脂肪生成基因的表达，有助于NAFLD和IR的改善。结论：RSV通过减少TG积累和改善IR，对NAFLD具有保护作用。AMPK的激活参与了这一机制。RSV具有预防或治疗NAFLD和ir相关代谢紊乱的治疗潜力。
Aim: To investigate whether resveratrol (RSV) can improve non-alcoholic fatty liver disease (NAFLD) and to find the possible mechanism. Methods: Rats fed a high-fat diet were treated with RSV. The liver histology was observed. Hyperinsulinemic euglycemic clamp was performed to assess insulin sensitivity. Fat accumulation was induced in HepG2 cells, and the cells were treated with RSV. AMP-activated protein kinase (AMPK) phosphorylation levels were determined both in the animal study and cell study. Results: Rats fed a high-fat diet developed abdominal obesity, NAFLD, and insulin resistance (IR), which were markedly improved by 10 weeks of RSV administration. RSV treatment prevented triacylglycerol (TG) accumulation in HepG2 cells that were incubated with high concentration of glucose and insulin. Both in vivo and in vitro studies showed that RSV treatment could promote the phosphorylation of AMPK, which in this study, suppressed 2 lipogenesis gene expressions, contributing to the improvement of NAFLD and IR. Conclusion: The results indicated that by reducing TG accumulation and improving IR, RSV could protect the liver from NAFLD. The activation of AMPK was involved in the mechanism. RSV has the therapeutic potential for preventing or treating NAFLD and IR-related metabolic disorders.