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PNAS:吃得少都发胖?这真得怪你的基因

2017-11-14 药明康德 学术经纬

最新一期《美国国家科学院院刊》(PNAS)上的一项研究,也许能让你找到减肥失败的好借口。杜克大学医学院(Duke University School of Medicine)的Vann Bennett教授与他的团队发现,不管你是否注重身材,一个简单的基因变异,就有可能让你更容易发胖!

我们常常将肥胖的原因归咎于自身——减肥一直不成功?主要是两大原因:管不住嘴,迈不开腿。如果摄入能量过多,运动又不足,脂肪自然就堆积起来。

不过,最新一期《美国国家科学院院刊》(PNAS)上的一项研究,也许能让你找到减肥失败的好借口。杜克大学医学院(Duke University School of Medicine)的Vann Bennett教授与他的团队发现,不管你是否注重身材,一个简单的基因变异,就有可能让你更容易发胖!

这个基因编码了一种叫做ankyrin-B的蛋白。有趣的是,早在30多年前,Bennett教授就找到了这个蛋白。它在身体的所有组织里都存在,能够把其他重要蛋白给拉到细胞里。之前,人们发现它与自闭症、肌营养不良症、衰老、糖尿病、以及心律不齐有关,没人意识到它居然还能影响肥胖。

直到几年前,一名叫做Jane Healey的细心博士生才意外发现,那些ankyrin-B带有变异而出现心律不齐的小鼠,看起来好像要比野生型的小鼠要胖。为了检验她的观察结果能否重复,Jane建立了一批小鼠的模型,里头编码ankyrin-B的基因带有几种常见的变异。

实验室里的博士后Damaris Lorenzo发现,这些小鼠果然脂肪增长得更快——它们更倾向于把卡路里锁在脂肪中,而不是送往身体其他地方燃烧产生能量。这个发现在2015年得到了发表。“然而,我们还是不知道这个基因是如何运作的,” Bennett教授说:“我们的通常信念是说肥胖由食欲引起,而控制食欲的中心在我们的大脑里。但如果肥胖不止是我们大脑控制的,又会怎样?”

如今已成为助理教授的Lorenzo博士做了进一步的研究。她的团队彻底敲除了小鼠脂肪组织里的ankyrin-B基因,然后观察小鼠生理上的异常。他们发现,尽管和普通小鼠的饮食与运动没有任何区别,这些ankyrin-B基因发生突变的小鼠,储存能量的白色脂肪细胞体积翻了个倍!而当他们成长时,体重也越容易增加。

“我们很快就意识到脂肪细胞内积聚的脂质会‘分散’到肝脏和肌肉里,” Lorenzo博士说道:“这些组织里的脂肪异常堆积会导致炎症,以及胰岛素响应的紊乱。这是2型糖尿病的标志。类似的信号通路在人体中经常发生,这就是为何肥胖对健康有害。”

进行了一系列生化实验后,Lorenzo博士与她的团队表明,ankyrin-B会影响到下游的Glut4,这是一种葡萄糖转移蛋白,能让葡萄糖进入脂肪细胞。一旦ankyrin-B发生变异,细胞就会向葡萄糖敞开大门,小鼠也就迅速肥胖起来。

“我们管这种肥胖叫做‘你没错’,” Bennett教授说:“我们相信这个基因可能帮助我们的祖先在饥荒时储存能量。但在食物充足的当下,这个基因变异就会导致肥胖流行。”

“我们发现小鼠不用吃多,就会变胖。而且背后有一套分子机制,” Bennett教授补充说:“这个基因能让我们找到那些容易长胖的高危人群。他们需要注意饮食,并多加锻炼,才能控制体重。”

接下来,研究人员想在人群里验证这个基因的影响。看到这里,你是不是也想去给自己的基因做个检测了呢?

原始出处:

Damaris N. Lorenzo and Vann Bennett.Cell-autonomous adiposity through increased cell surface GLUT4 due to ankyrin-B deficiency.Proc Natl Acad Sci U S A.published ahead of print November 13, 2017.

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    2018-02-01 drwjr
  2. [GetPortalCommentsPageByObjectIdResponse(id=1856090, encodeId=d00718560907a, content=<a href='/topic/show?id=f32014428fc' target=_blank style='color:#2F92EE;'>#PNAS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14428, encryptionId=f32014428fc, topicName=PNAS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=08e964, createdName=drwjr, createdTime=Thu Feb 01 08:01:00 CST 2018, time=2018-02-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=264385, encodeId=66152643852a, content=学习一下谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=71, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mONcle9pic3zMoyicyo6ia9f4IuLQAwZoxD6Hx4ibd5CMcOCYhStY6oDibbKK6O2X8iaicldO5ib8j1iapOIobIKCGiczU2A/0, createdBy=56251941490, createdName=虈亣靌, createdTime=Sun Nov 26 07:30:09 CST 2017, time=2017-11-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=261444, encodeId=434c261444df, content=好好看下.内容丰富, beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mONcle9pic3zMoyicyo6ia9f4IuLQAwZoxD6Hx4ibd5CMcOCYhStY6oDibbKK6O2X8iaicldO5ib8j1iapOIobIKCGiczU2A/0, createdBy=56251941490, createdName=虈亣靌, createdTime=Wed Nov 15 13:22:43 CST 2017, time=2017-11-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=261270, encodeId=e1b12612e0c4, content=学习一下谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzaiabIFicf63hKvVMjL6aJlx4yX4UcXmzX9DyibCRcicq0QtCRWMaQKh8MYjE1D3EKUBopgiaGWYuqbeR/0, createdBy=0c2b1999806, createdName=三生有幸9135, createdTime=Tue Nov 14 16:20:40 CST 2017, time=2017-11-14, status=1, ipAttribution=)]
    2017-11-26 虈亣靌

    学习一下谢谢分享

    0

  3. [GetPortalCommentsPageByObjectIdResponse(id=1856090, encodeId=d00718560907a, content=<a href='/topic/show?id=f32014428fc' target=_blank style='color:#2F92EE;'>#PNAS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14428, encryptionId=f32014428fc, topicName=PNAS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=08e964, createdName=drwjr, createdTime=Thu Feb 01 08:01:00 CST 2018, time=2018-02-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=264385, encodeId=66152643852a, content=学习一下谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=71, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mONcle9pic3zMoyicyo6ia9f4IuLQAwZoxD6Hx4ibd5CMcOCYhStY6oDibbKK6O2X8iaicldO5ib8j1iapOIobIKCGiczU2A/0, createdBy=56251941490, createdName=虈亣靌, createdTime=Sun Nov 26 07:30:09 CST 2017, time=2017-11-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=261444, encodeId=434c261444df, content=好好看下.内容丰富, beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mONcle9pic3zMoyicyo6ia9f4IuLQAwZoxD6Hx4ibd5CMcOCYhStY6oDibbKK6O2X8iaicldO5ib8j1iapOIobIKCGiczU2A/0, createdBy=56251941490, createdName=虈亣靌, createdTime=Wed Nov 15 13:22:43 CST 2017, time=2017-11-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=261270, encodeId=e1b12612e0c4, content=学习一下谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzaiabIFicf63hKvVMjL6aJlx4yX4UcXmzX9DyibCRcicq0QtCRWMaQKh8MYjE1D3EKUBopgiaGWYuqbeR/0, createdBy=0c2b1999806, createdName=三生有幸9135, createdTime=Tue Nov 14 16:20:40 CST 2017, time=2017-11-14, status=1, ipAttribution=)]
    2017-11-15 虈亣靌

    好好看下.内容丰富

    0

  4. [GetPortalCommentsPageByObjectIdResponse(id=1856090, encodeId=d00718560907a, content=<a href='/topic/show?id=f32014428fc' target=_blank style='color:#2F92EE;'>#PNAS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14428, encryptionId=f32014428fc, topicName=PNAS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=08e964, createdName=drwjr, createdTime=Thu Feb 01 08:01:00 CST 2018, time=2018-02-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=264385, encodeId=66152643852a, content=学习一下谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=71, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mONcle9pic3zMoyicyo6ia9f4IuLQAwZoxD6Hx4ibd5CMcOCYhStY6oDibbKK6O2X8iaicldO5ib8j1iapOIobIKCGiczU2A/0, createdBy=56251941490, createdName=虈亣靌, createdTime=Sun Nov 26 07:30:09 CST 2017, time=2017-11-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=261444, encodeId=434c261444df, content=好好看下.内容丰富, beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mONcle9pic3zMoyicyo6ia9f4IuLQAwZoxD6Hx4ibd5CMcOCYhStY6oDibbKK6O2X8iaicldO5ib8j1iapOIobIKCGiczU2A/0, createdBy=56251941490, createdName=虈亣靌, createdTime=Wed Nov 15 13:22:43 CST 2017, time=2017-11-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=261270, encodeId=e1b12612e0c4, content=学习一下谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzaiabIFicf63hKvVMjL6aJlx4yX4UcXmzX9DyibCRcicq0QtCRWMaQKh8MYjE1D3EKUBopgiaGWYuqbeR/0, createdBy=0c2b1999806, createdName=三生有幸9135, createdTime=Tue Nov 14 16:20:40 CST 2017, time=2017-11-14, status=1, ipAttribution=)]
    2017-11-14 三生有幸9135

    学习一下谢谢分享

    0

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