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Mol Cell Endocrinol :弱骨强代谢——指向糖尿病的新治疗

2015-06-17 佚名 生物谷

骨骼脆弱显然不是一件好事,不过科学家们怀疑,基因工程小鼠的骨骼和身体的其余部分之间的某处联系中,可能隐藏了一个答案,能够帮助肥胖者避免一些由肥胖带来的健康困扰。佐治亚大学医学院的研究人员最近报告说,拥有脆弱骨骼的小鼠有很强的代谢能力,即使是在高脂肪饮食条件下。这篇研究发表在最近的Molecular and Cellular Endocrinology杂志。 McGee-Lawrence博士是该研

骨骼脆弱显然不是一件好事,不过科学家们怀疑,基因工程小鼠的骨骼和身体的其余部分之间的某处联系中,可能隐藏了一个答案,能够帮助肥胖者避免一些由肥胖带来的健康困扰。佐治亚大学医学院的研究人员最近报告说,拥有脆弱骨骼的小鼠有很强的代谢能力,即使是在高脂肪饮食条件下。这篇研究发表在最近的Molecular and Cellular Endocrinology杂志。

McGee-Lawrence博士是该研究的第一作者,她说道:“我们都知道骨头对于生物运动力学、保护内脏器官和储存身体内的钙都是很重要的。但在过去10年左右,人们才真正开始明白骨骼的功能远超过这些。事实上,它是体内有一个非常重要的内分泌作用。”骨的代谢影响被她定义为“新边界”,而骨代谢的研究对于得到完整骨骼作用的答案很重要。确定骨作为一个内分泌器官的证据将指向对肥胖有关的2型糖尿病进行干预的新方法。

McGee-Lawrence重点研究的是分子HDAC3,它是分布在体内的调控基因表达的一个重要调控子,可使得基因表达上升或下降。当研究小组在骨骼中删除HDAC3,他们并不惊讶地发现小鼠的骨骼表现较弱。不过惊奇地是,小鼠的主要代谢能力也随之调整。尽管基因敲除的小鼠进食量与对照相比正常,但它们有较少的体脂肪和较低的空腹葡萄糖水平,葡萄糖使用的效率增高,而且胰岛素的使用也更有效(靶向器官的敏感度增加)。2型糖尿病的小鼠和人类的症状中,其中一个就是肝脏的胰岛素敏感性降低。而HDAC3敲除的小鼠肝脏对胰岛素非常敏感。

研究人员开始寻找导致这个表型的“嫌疑者”。骨钙素,是由成骨细胞生产,是已知的最被认可能够影响胰岛素分泌和灵敏度的骨源性分子。可是他们在敲除的老鼠身上发现,骨钙素水平比对照反而更低。

随后他们转向肝脏。肝脏对于消化,管理代谢和储存能量有重要意义。既然HDAC3敲除小鼠有更好的新陈代谢率,那到底是骨中的什么物质,与肝脏沟通改变了代谢?研究人员怀疑是有助于肝脏保持健康的胰岛素敏感性的一种分子,这个分子可能是骨保护素(osteoprotegerin,OPG)。OPG也由成骨细胞分泌,能保护降低骨中的骨分解量。这个分子的功能被模仿制成药物狄诺塞麦,新一代骨质疏松症的药物之一。

HDAC3基因敲除小鼠表现出高水平的OPG。除了它在骨架的作用,OPG可以在血液中运输到肝脏,减少炎症。减少肝脏炎症意义着胰岛素敏感性的改善,这使OPG成了一个有力的“嫌疑者”。如果OPG的确是代谢增加的原因,这可能意味着一种现有的药物将能直接解决肥胖这种可预防的疾病,甚至包括2型糖尿病和心血管等。

原始出处:

Meghan E. McGee-Lawrence, 1, , Thomas A. White, Nathan K. LeBrasseur, Jennifer J. Westendorf.Meghan E. McGee-Lawrence, 1, , Thomas A. White, Nathan K. LeBrasseur, Jennifer J. Westendorf.Conditional deletion of Hdac3 in osteoprogenitor cells attenuates diet-induced systemic metabolic dysfunction.Molecular & Cellular Endocrinology, July 15, 2015.doi:10.1016/j.mce.2015.02.001

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    2015-09-09 Bobby7868

    很新颖,赞

    0

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    2015-07-12 文刀

    够拿诺贝尔了,解决肥胖和二型dm

    0

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    2015-06-29 cyzj007

    太牛逼了吧!

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=1869142, encodeId=51861869142c9, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=69, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Mon Dec 28 22:07:00 CST 2015, time=2015-12-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1959396, encodeId=5be91959396ed, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4dfa37, createdName=智者为医08, createdTime=Sat Mar 12 11:07:00 CST 2016, time=2016-03-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=36564, encodeId=a25a36564f5, content=很新颖,赞, beContent=null, objectType=article, channel=null, level=null, likeNumber=148, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=75bb1617091, createdName=Bobby7868, createdTime=Wed Sep 09 13:32:00 CST 2015, time=2015-09-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=32509, encodeId=6ccd32509c0, content=够拿诺贝尔了,解决肥胖和二型dm, beContent=null, objectType=article, channel=null, level=null, likeNumber=194, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20150707/IMG559BDBCBCA5618647.jpg, createdBy=494c1631012, createdName=文刀, createdTime=Sun Jul 12 20:18:00 CST 2015, time=2015-07-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=29969, encodeId=0d9f2996927, content=太牛逼了吧!, beContent=null, objectType=article, channel=null, level=null, likeNumber=139, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20150625/IMG558B8C995D7262168.jpg, createdBy=36ad1623080, createdName=cyzj007, createdTime=Mon Jun 29 23:17:00 CST 2015, time=2015-06-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=29268, encodeId=ed26292689f, content=看看, beContent=null, objectType=article, channel=null, level=null, likeNumber=161, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ee0d1618732, createdName=huaxipanxing, createdTime=Thu Jun 25 23:16:00 CST 2015, time=2015-06-25, status=1, ipAttribution=)]
    2015-06-25 huaxipanxing

    看看

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