3-Acetyl-oleanolic acid ameliorates non-alcoholic fatty liver disease in high fat diet-treated rats by activating AMPK-related pathways
3-Acetyl-oleanolic acid ameliorates non-alcoholic fatty liver disease in high fat diet-treated rats by activating AMPK-related pathways
复制标题
3-乙酰齐墩果酸通过激活 AMPK 相关途径改善高脂饮食治疗大鼠的非酒精性脂肪肝
DOI：
10.1038/aps.2017.142
复制
发表时间：
2018-08-01
影响因子：
8.2
通讯作者：
Liu, Jun
中科院分区：
文献类型：
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作者：
Ou-Yang, Qiong;Xuan, Chun-xiao;Liu, Jun
3-乙酰基-油酸（3Ac-OA）是油酸（OA）的衍生物，其对糖尿病和代谢综合征显示出有益的治疗作用。在这项研究中，我们研究了3Ac-OA是否对大鼠非酒精性脂肪性肝病（NAFLD）产生有益作用及其潜在的潜在机制。3Ac-OA（1-100 μmol/L）可剂量依赖性地降低FFA处理的原代大鼠肝细胞和人HepG 2细胞内总胆固醇（TC）和甘油三酯（TG）水平。此外，油红染色研究表明，3Ac-OA引起FFA处理的原代大鼠肝细胞中脂滴数量的剂量依赖性减少。高脂饲料喂养SD大鼠6周后，分别给予3Ac-OA（60、30、15 mg· kg-1· d-1）治疗4周。3Ac-OA能显著降低HFD大鼠的体重、肝重和血清TC、TG、LDL-C水平。此外，3AcOA给药改善了HFD大鼠肝脏中的脂质积聚和细胞凋亡。使用脂肪因子阵列分析，我们发现11种脂肪因子（HGF、ICAM、IGF-1、IGFBP-3、IGFBP-5、IGFBP-6、脂质运载蛋白-2、MCP-1、M-CSF、Pref-1和Lipocalin-2）的水平在3Ac-OA处理的大鼠的血清中增加超过2倍，而ICAM、IGF-1和脂质运载蛋白-2的水平增加超过20倍。此外，3 Ac-OA给药还显著增加了HFD大鼠肝组织中葡萄糖转运蛋白2（GLUT-2）和低密度脂蛋白受体（LDLR）的表达，以及AMP活化蛋白激酶（AMPK）、蛋白激酶B（AKT）和糖原合成酶激酶3β（GSK-3β）的磷酸化。总之，本研究表明，3Ac-OA通过AMPK相关途径对NAFLD大鼠的高脂血症发挥保护作用。
3-Acetyl-oleanolic acid (3Ac-OA) is a derivative of oleanolic acid (OA), which has shown therapeutic beneficial effects on diabetes and metabolic syndrome. In this study we investigated whether 3Ac-OA exerted beneficial effect on non-alcoholic fatty liver disease (NAFLD) in rats and its potential underlying mechanisms. Treatment with 3Ac-OA (1–100 μmol/L) dose-dependently decreased the intracellular levels of total cholesterol (TC) and triglyceride (TG) in FFA-treated primary rat hepatocytes and human HepG2 cell lines in vitro. Furthermore, oil red staining studies showed that 3Ac-OA caused dose-dependent decrease in the number of lipid droplets in FFA-treated primary rat hepatocytes. SD rats were fed a high fat diet (HFD) for 6 weeks and subsequently treated with 3Ac-OA (60, 30, 15 mg· kg-1· d-1) for 4 weeks. 3Ac-OA administration significantly decreased the body weight, liver weight and serum TC, TG, LDL-C levels in HFD rats. Furthermore, 3AcOA administration ameliorated lipid accumulation and cell apoptosis in the liver of HFD rats. Using adipokine array analyses, we found that the levels of 11 adipokines (HGF, ICAM, IGF-1, IGFBP-3, IGFBP-5, IGFBP-6, lipocalin-2, MCP-1, M-CSF, Pref-1 and RAGE) were increased by more than twofold in the serum of 3Ac-OA-treated rats, whereas ICAM, IGF-1 and lipocalin-2 had levels increased by more than 20-fold. Moreover, 3Ac-OA administration significantly increased the expression of glucose transporter type 2 (GLUT-2) and low-density lipoprotein receptor (LDLR), as well as the phosphorylation of AMP-activated protein kinase (AMPK), protein kinase B (AKT) and glycogen synthase kinase 3β (GSK-3β) in the liver tissues of HFD rats. In conclusion, this study demonstrates that 3Ac-OA exerts a protective effect against hyperlipidemia in NAFLD rats through AMPK-related pathways.