Gut:miRNA-132通过协同多靶点抑制,促进肝脂肪变性和高脂血症

2018-06-22 MedSci MedSci原创

研究发现,miR-132是肝脏脂质稳态的关键调控因子,通过抑制多个靶点和累积协同效应,以环境依赖性的方式发挥作用。这表明降低miR-132水平可能治疗肝脂肪变性。

研究目的:非酒精性脂肪肝(NAFLD)和microRNA (miR)抑制的多靶点复杂性最近引起了较多关注。但对肝脏miR-靶向相互作用的体内影响和环境依赖性尚未完全了解。本研究旨在评估特定靶点在体内对miR介导表型的相对贡献。

研究方法:研究在过表达miR-132的转基因小鼠、NAFLD患者的肝脏组织以及不同的肝脂肪变性小鼠模型中量化了脂肪肝参数和miR-132及其靶点的水平。在饮食诱导的小鼠中,注射miR-132的反义寡核苷酸抑制因子和miR-132目标基因,检测代谢参数和转录表达的改变。

研究结果:过表达miR-132的转基因小鼠表现为严重的脂肪肝,体重增加,血清低密度脂蛋白/极低密度脂蛋白(LDL/VLDL)和三甘油三酯升高,同时miR-132靶点降低,脂肪生成和脂质积累相关转录本增加。同样,NAFLD患者、肝脂肪变性、非酒精性脂肪肝炎(NASH)小鼠模型等的肝脏样本表明,与对照组肝脏相比,miR-132表达显著增加,而miR-132的靶点则有不同程度的下降。此外,注射抗miR-132寡核苷酸的饮食诱导的肥胖小鼠,不抑制其单个靶点,逆转了肝脏miR-132的过量和高血脂表型。

研究结论:研究发现,miR-132是肝脏脂质稳态的关键调控因子,通过抑制多个靶点和累积协同效应,以环境依赖性的方式发挥作用。这表明降低miR-132水平可能治疗肝脂肪变性。

原始出处:

Hanin G, Yayon N, Tzu Y, et al. miRNA-132 induces hepatic steatosis and hyperlipidaemia by synergistic multitarget suppression. Gut, 2018, 67(6), 1124-1134.

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    2019-01-10 zhangph
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ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=326170, encodeId=d1563261e08d, content=学习了谢谢分享!!, beContent=null, objectType=article, channel=null, level=null, likeNumber=67, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20200816/e4675a86ea694f12b82202b320dc2654/12f6b900498349e994ce8f516a584d6a.jpg, createdBy=09431951290, createdName=大爰, createdTime=Fri Jun 22 21:38:49 CST 2018, time=2018-06-22, status=1, ipAttribution=)]
    2018-07-06 smallant2002
  5. 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ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=326170, encodeId=d1563261e08d, content=学习了谢谢分享!!, beContent=null, objectType=article, channel=null, level=null, likeNumber=67, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20200816/e4675a86ea694f12b82202b320dc2654/12f6b900498349e994ce8f516a584d6a.jpg, createdBy=09431951290, createdName=大爰, createdTime=Fri Jun 22 21:38:49 CST 2018, time=2018-06-22, status=1, ipAttribution=)]
    2018-06-24 Homburg
  6. 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ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=326170, encodeId=d1563261e08d, content=学习了谢谢分享!!, beContent=null, objectType=article, channel=null, level=null, likeNumber=67, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20200816/e4675a86ea694f12b82202b320dc2654/12f6b900498349e994ce8f516a584d6a.jpg, createdBy=09431951290, createdName=大爰, createdTime=Fri Jun 22 21:38:49 CST 2018, time=2018-06-22, status=1, ipAttribution=)]
    2018-06-24 huangdf
  7. 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ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=326170, encodeId=d1563261e08d, content=学习了谢谢分享!!, beContent=null, objectType=article, channel=null, level=null, likeNumber=67, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20200816/e4675a86ea694f12b82202b320dc2654/12f6b900498349e994ce8f516a584d6a.jpg, createdBy=09431951290, createdName=大爰, createdTime=Fri Jun 22 21:38:49 CST 2018, time=2018-06-22, status=1, ipAttribution=)]
    2018-06-24 pcw111
  9. 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    2018-06-22 changjiu

    学习一下谢谢

    0

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    2018-06-22 大爰

    学习了谢谢分享!!

    0

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