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.

中文翻译：

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3-乙酰基油酸可通过激活AMPK相关途径改善高脂饮食治疗大鼠的非酒精性脂肪肝疾病。

3-乙酰基油酸（3Ac-OA）是齐墩果酸（OA）的衍生物，已显示出对糖尿病和代谢综合征的治疗有益作用。在这项研究中，我们调查了3Ac-OA是否对大鼠非酒精性脂肪肝疾病（NAFLD）发挥有益作用及其潜在的潜在机制。用3Ac-OA（1-100μmol/ L）剂量依赖性地降低了经FFA处理的原代大鼠肝细胞和人HepG2细胞系中的总胆固醇（TC）和甘油三酸酯（TG）的细胞内水平。此外，油红染色研究表明3Ac-OA导致了FFA处理的原代大鼠肝细胞中脂滴数量的剂量依赖性下降。SD大鼠接受高脂饮食（HFD）6周，然后用3Ac-OA（60、30、15 mg·kg ^-1 ·d ^-1），持续4周。3Ac-OA给药可显着降低HFD大鼠的体重，肝脏重量和血清TC，TG，LDL-C水平。此外，3AcOA给药改善了HFD大鼠肝脏中的脂质蓄积和细胞凋亡。使用脂肪因子阵列分析，我们发现了11种脂肪因子（HGF，ICAM，IGF-1，IGFBP-3，IGFBP-5，IGFBP-6，lipocalin-2，MCP-1，M-CSF，Pref-1和RAGE）在3Ac-OA治疗的大鼠血清中增加了两倍以上，而ICAM，IGF-1和lipocalin-2的水平增加了20倍以上。此外，施用3Ac-OA可以显着增加2型葡萄糖转运蛋白（GLUT-2）和低密度脂蛋白受体（LDLR）的表达，以及AMP激活的蛋白激酶（AMPK）的磷酸化，HFD大鼠肝脏组织中的蛋白激酶B（AKT）和糖原合酶激酶3β（GSK-3β）。总之，这项研究表明3Ac-OA通过AMPK相关途径对NAFLD大鼠高脂血症具有保护作用。