Cell子刊:服用激活cGMP信号的药物降低体重有戏!

2017-01-07 佚名 生物谷

在一项新的研究中,来自德国波恩大学的研究人员在小鼠体内证实通过将不想要的白色脂肪细胞转化为消耗能量的褐色脂肪细胞就能够减掉超重的体重。这种有趣的方法也能够被用来抵抗肥胖吗?他们证实经常在体重超重的人体内发生的炎性反应会抑制这种类型的脂肪细胞转换。然而,可能存在一种绕过这种抑制的起始点。相关研究结果发表在2017年1月3日那期Cell Reports期刊上,论文标题为“Interplay betw


在一项新的研究中,来自德国波恩大学的研究人员在小鼠体内证实通过将不想要的白色脂肪细胞转化为消耗能量的褐色脂肪细胞就能够减掉超重的体重。这种有趣的方法也能够被用来抵抗肥胖吗?他们证实经常在体重超重的人体内发生的炎性反应会抑制这种类型的脂肪细胞转换。然而,可能存在一种绕过这种抑制的起始点。相关研究结果发表在2017年1月3日那期Cell Reports期刊上,论文标题为“Interplay between Obesity-Induced Inflammation and cGMP Signaling in White Adipose Tissue”。

前景是诱人的:如果利用新的活性成分能够简单地减掉身体脂肪的话,那么这也可能阻肥胖的普遍后果,如关节问题、糖尿病和心血管疾病。波恩大学药理学与毒理学研究所的Alexander Pfeifer团队多年来一直在研究这如何才是可能的。Pfeifer报道,“在针对小鼠的研究中,我们发现将讨厌的白色脂肪细胞转化为想要的褐色脂肪细胞的多种起始点。”这些褐色脂肪细胞拥有非常高数量的线粒体:这些细胞能量工厂(即线粒体)通过将白色脂肪转化为热能而将它“燃烧掉”。结果就是:如果褐色脂肪细胞数量增加,那么这些小鼠显著地减轻体重。

信使环鸟苷酸(cGMP)信号通路在这种脂肪转换中发挥着重要的作用。Pfeifer解释道,“这种褐色脂肪细胞依赖于cGMP。”正如研究人员在小鼠体内开展的多项研究所证实的那样,广泛使用的活性成分西地那非或者一种治疗肺动脉高血压的药物能够被用来降低白色脂肪细胞的数量而有利于褐色脂肪细胞,因而像涡轮增压器那样加快脂肪燃烧。

在腹部脂肪中,脂肪燃烧涡轮增压器陷入停滞

这是一种有效地治疗全世界显著增加的肥胖水平因而阻止严重并发症的可行性选择吗?这正是研究人员在他们当前的这项研究中正在探究的问题。他们给小鼠喂食高能量的食物,检查它们的脂肪组织发生的变化。尽管肥胖小鼠的皮下脂肪几乎没有任何炎症产生,而且cGMP信号通路大体上保持完整,但是对埋藏在深处的腹部脂肪来说,情形却大为不同:因为显著的体重增加,炎症已扩散开来,而且作为脂肪燃烧的涡轮增压器,cGMP信号通路基本上陷入停滞。

这揭示了一个对偶问题(dual problem):腹部脂肪被认为比皮下脂肪更加危险,这是因为前者促发炎症产生,而且能够引发心血管疾病等有害的后果。根据波恩大学研究人员的最新研究结果,这也正是cGMP基本上被阻断的地方。他们因此自问:有可能移除这种阻断吗?

论文第一作者、Pfeifer团队成员Abhishek Sanyal研究了这个问题。他研究了炎症以何种方式抑制cGMP信号通路。Sanyal报道,“肿瘤坏死因子α(TNFα)在其中发挥着重要作用。炎症因子TNFα抑制cGMP信号通路,因而阻断白色脂肪细胞转化为褐色脂肪细胞。”

通过与来自德国莱比锡大学医院和瑞典斯德哥尔摩卡罗琳斯卡研究所的研究人员合作,波恩大学研究人员利用人皮下脂肪和腹部脂肪样品,发现类似的变化不仅存在于啮齿类动物体内,而且也存在于人体内。尽管人类肥胖治疗的应用仍然遥遥无期,但是这些结果指明了一种进一步开展研究的方向。Pfeifer在总结这些发现时说道,“明显地,抵抗肥胖的一个可能的起始点是通过服用激活cGMP的活性成分抑制腹部脂肪中的炎性反应。”

原始出处

Abhishek Sanyal, Jennifer Naumann, Linda Sarah Hoffmann8, Agnieszka Chabowska-Kita, Anna Ehrlund, Andreas Schlitzer, Peter Arner, Matthias Blüher, Alexander Pfeifer.Interplay between Obesity-Induced Inflammation and cGMP Signaling in White Adipose Tissue.Cell Reports.2016

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    2017-01-10 zhishijing
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    2017-11-02 维他命
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    2017-01-12 清幽蓝燕yan

    值得学习!

    0

  5. [GetPortalCommentsPageByObjectIdResponse(id=2050100, encodeId=bf0b205010058, content=<a href='/topic/show?id=4691454e37' target=_blank style='color:#2F92EE;'>#CGM#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4547, encryptionId=4691454e37, topicName=CGM)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5d70341, createdName=zhishijing, createdTime=Tue Jan 10 18:56:00 CST 2017, time=2017-01-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1869723, encodeId=aebc1869e23a9, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Wed Aug 09 00:56:00 CST 2017, time=2017-08-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1959982, encodeId=f2741959982f3, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Thu Nov 02 17:56:00 CST 2017, time=2017-11-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=169952, encodeId=8caf169952c8, content=值得学习!, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTJHmctib8wsjB1Y0etxU20nsCbR8rZ2fpibp2STmwH2YzicIsTe9oHRGB6XIMeBqNdIvxODicmzfeQibIw/132, createdBy=82211964557, createdName=清幽蓝燕yan, createdTime=Thu Jan 12 23:40:42 CST 2017, time=2017-01-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=169649, encodeId=78591696498d, content=值得期待, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6KcicAVC1MwuOgo3iaicb1Imgk1yIfnvr6oXzibcAFB6puAyNJXbzWhNuLqaFYBVRWjh7rghkvFLPxMAfD5ib3nXwVD/0, createdBy=bed21972958, createdName=wxl882001, createdTime=Wed Jan 11 19:16:43 CST 2017, time=2017-01-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1376685, encodeId=bded13e668538, content=<a href='/topic/show?id=30488132aa' target=_blank style='color:#2F92EE;'>#GMP#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8132, encryptionId=30488132aa, topicName=GMP)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8c6f389, createdName=hxq78316, createdTime=Mon Jan 09 04:56:00 CST 2017, time=2017-01-09, status=1, ipAttribution=)]
    2017-01-11 wxl882001

    值得期待

    0

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    2017-01-09 hxq78316