• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>The Journal of Nutritional Biochemistry >Nonalcoholic fatty liver disease is associated with an altered hepatocyte microRNA profile in LDL receptor knockout mice.
【24h】

Nonalcoholic fatty liver disease is associated with an altered hepatocyte microRNA profile in LDL receptor knockout mice.

机译：非酒精性脂肪肝疾病与LDL受体敲除小鼠肝细胞microRNA谱改变有关。

获取原文
获取原文并翻译 | 示例
       
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

MicroRNAs modulate processes associated with cell cycle control and differentiation. Here we explored the potential of microRNAs in the modulation of hepatic lipid metabolism and the development of nonalcoholic fatty liver disease. MicroRNA profiles of hepatocytes from low-density lipoprotein (LDL) receptor knockout mice fed a chow diet or a hypertriglyceridemia/fatty liver-inducing Western-type diet (WTD) were determined using quantitative real-time polymerase chain reaction. Ninety-seven of 103 microRNAs measured were expressed by hepatocytes and low variability between hepatocyte pools was observed. Feeding WTD coincided with a marked fivefold decrease in the relative expression level of miR-216 (P<.05) and miR-302a (P<.01). Interestingly, an increased hepatic miR-216 expression was detected in response to fasting. MicroRNA/biological function linkage analysis suggested that the change in hepatocyte microRNA profiles in response to high dietary lipid levels is associated with changes in cell cycle control and proliferation. In accordance with a diminished miR-302a expression on the WTD, hepatocyte mRNA expression levels of miR-302a target genes ABCA1 and in particular ELOVL6 were increased in response to WTD (twofold to ninefold). This suggests a role for miR-302a in hepatic cholesterol, fatty acid and glucose metabolism. In conclusion, we have shown that fatty liver development in LDL receptor knockout mice is associated with a significant change in the hepatocyte microRNA profile, i.e., a fivefold decrease in miR-216 and miR-302a expression. Based upon our comparative gene and microRNA expression studies it is anticipated that miR-302a may prove to be a valuable therapeutic target in the regulation of hepatic fatty acid utilization and insulin resistance
机译：MicroRNA调节与细胞周期控制和分化相关的过程。在这里，我们探讨了微RNA在调节肝脂质代谢和非酒精性脂肪肝疾病发展中的潜力。使用定量实时聚合酶链反应确定了喂低脂饮食或高甘油三酯血症/脂肪肝诱导型西式饮食（WTD）的低密度脂蛋白（LDL）受体敲除小鼠的肝细胞MicroRNA谱。所测量的103个microRNA中有97个由肝细胞表达，并且观察到肝细胞库之间的变异性较低。喂食WTD与miR-216（P <.05）和miR-302a（P <.01）的相对表达水平显着降低了五倍。有趣的是，检测到对禁食的肝miR-216表达增加。 MicroRNA /生物学功能连锁分析表明，响应高饮食脂质水平的肝细胞microRNA图谱的变化与细胞周期控制和增殖的变化有关。根据WTD上miR-302a的表达减少，miR-302a靶基因ABCA1特别是ELOVL6的肝细胞mRNA表达水平响应WTD而增加（两倍至九倍）。这表明miR-302a在肝胆固醇，脂肪酸和葡萄糖代谢中的作用。总之，我们已经表明，LDL受体敲除小鼠的脂肪肝发育与肝细胞microRNA谱的显着变化有关，即miR-216和miR-302a表达降低了五倍。根据我们的比较基因和microRNA表达研究，可以预期miR-302a可能被证明是调节肝脂肪酸利用和胰岛素抵抗的有价值的治疗靶标

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号