Department of Food and Nutrition, Brain Korea 21 Project, Yonsei University, 262 Seongsanno, Seodaemun-gu, Seoul 120-749, Republic of Korea.
J Hepatol. 2011 May;54(5):984-93. doi: 10.1016/j.jhep.2010.08.019. Epub 2010 Oct 31.
BACKGROUND & AIMS: Oleuropein, a secoiridoid derived from olives and olive oil, has been known to possess antimicrobial, antioxidative, and anticancer activities. The purpose of the present study was to determine whether oleuropein has a protective effect against hepatic steatosis induced by a high fat diet (HFD) and to elucidate its underlying molecular mechanisms in mice.
Male C57BL/6N mice were fed a normal diet (ND), HFD, or an oleuropein-supplemented diet (OSD) for 10 weeks. The plasma and hepatic lipid levels were determined, and the hepatic gene and protein expression levels were analysed via RT-PCR and Western blotting, respectively.
The supplementation of HFD with oleuropein reversed the HFD-induced increases in liver weight along with plasma and hepatic lipid levels in mice. The expression of Wnt10b inhibitor genes, such as secreted firizzed-related sequence protein 5 and dickkopf homolog 2, was downregulated, whereas the β-catenin protein expression was upregulated in the liver of OSD-fed mice compared to HFD-fed mice. Fibroblast growth factor receptor 1 (FGFR1), phosphoextracellular-signal-regulated kinase 1/2, cyclin D, and E2F transcription factor 1, along with several key transcription factors and their target genes involved in adipogenesis, were downregulated by oleuropein. OSD-fed mice exhibited decreased expression of the toll-like-receptor-(TLR)-mediated signaling molecules (TLR2, TLR4, and myeloid differentiation primary-response gene 88) and proinflammatory cytokines, in their livers, as compared to HFD mice.
These results suggest that the protective effects of oleuropein against HFD-induced hepatic steatosis in mice appear to be associated with the Wnt10b- and FGFR1-mediated signaling cascades involved in hepatic lipogenesis, along with the TLR2- and TLR4-mediated signaling implicated in hepatic steatosis.
橄榄苦苷是一种从橄榄和橄榄油中提取的次级环烯醚萜，具有抗菌、抗氧化和抗癌活性。本研究旨在确定橄榄苦苷是否对高脂肪饮食（HFD）诱导的肝脂肪变性具有保护作用，并阐明其在小鼠中的潜在分子机制。
雄性 C57BL/6N 小鼠分别喂食正常饮食（ND）、HFD 或添加橄榄苦苷的饮食（OSD）10 周。测定血浆和肝脂质水平，并通过 RT-PCR 和 Western blot 分别分析肝基因和蛋白表达水平。
HFD 中添加橄榄苦苷可逆转 HFD 诱导的小鼠肝重增加以及血浆和肝脂质水平升高。与 HFD 组相比，OSD 组小鼠肝脏中 Wnt10b 抑制剂基因（如分泌卷曲相关序列蛋白 5 和 Dickkopf 同源物 2）的表达下调，β-连环蛋白蛋白表达上调。纤维母细胞生长因子受体 1（FGFR1）、磷酸细胞外信号调节激酶 1/2、细胞周期蛋白 D 和 E2F 转录因子 1 以及参与脂肪生成的几个关键转录因子及其靶基因的表达被橄榄苦苷下调。与 HFD 组相比，OSD 组小鼠肝脏中 TLR 介导的信号分子（TLR2、TLR4 和髓样分化初级反应基因 88）和促炎细胞因子的表达降低。
这些结果表明，橄榄苦苷对 HFD 诱导的小鼠肝脂肪变性的保护作用可能与涉及肝脂肪生成的 Wnt10b 和 FGFR1 介导的信号级联以及 TLR2 和 TLR4 介导的肝脂肪变性有关。
