Hepatology：GLP-1受体激动剂改善脂肪肝时肝脏内质网应激新机制

2017-12-20 曾龙驿中山大学新闻网

<div>由广东省<a class="channel_keylink" href="http://www.medsci.cn/article/list.do?q=%E7%B3%96%E5%B0%BF%E7%97%85">糖尿病</a>防治重点实验室、中山大学附属第三医院内分泌与代谢病学科翁建平教授团队独立完成的关于“GLP-1受体激动剂调控脂毒性所致肝脏内质网应激的机制研究”取得新进展，相关研究结果在Hepatology杂志上发表，题目为：SIRT1/HSF1/HSP pathway is essential for exenatide-alleviated， lipid-induced hepatic endoplasmic reticulum stress。</div><div><br></div><div>随着肥胖症的普遍流行，非酒精性脂肪性肝病（NAFLD）已迅速发展为全世界范围内最常见的慢性肝脏疾病，严重威胁人类的健康。肝脏脂质沉积是NAFLD的基础病变及代谢组分，可导致并加重肝脏内质网应激；而内质网应激可通过上调脂质从头合成而促进肝脏脂质沉积的进展，二者形成恶性循环。翁建平

由广东省糖尿病防治重点实验室、中山大学附属第三医院内分泌与代谢病学科翁建平教授团队独立完成的关于“GLP-1受体激动剂调控脂毒性所致肝脏内质网应激的机制研究”取得新进展，相关研究结果在Hepatology杂志上发表，题目为：SIRT1/HSF1/HSP pathway is essential for exenatide-alleviated， lipid-induced hepatic endoplasmic reticulum stress。

随着肥胖症的普遍流行，非酒精性脂肪性肝病（NAFLD）已迅速发展为全世界范围内最常见的慢性肝脏疾病，严重威胁人类的健康。肝脏脂质沉积是NAFLD的基础病变及代谢组分，可导致并加重肝脏内质网应激；而内质网应激可通过上调脂质从头合成而促进肝脏脂质沉积的进展，二者形成恶性循环。翁建平教授团队的前期研究（Diabetes. 2014 Nov；63(11)：3637-46.）已证实GLP-1受体激动剂艾塞那肽除降低血糖外，还可显着改善肝脏的脂质沉积，并且其机制由去乙酰化酶SIRT1介导。然而，GLP-1受体激动剂对脂毒性所致肝脏内质网应激的作用及机制尚不明确，最新的这项研究即探讨了其调控脂肪肝状态下脂毒性肝脏内质网应激的具体分子机制。

脂肪肝状态下，内质网应激与脂质沉积互为因果、形成恶性循环，因此调控内质网应激对于能否打破此恶性循环具有至关重要的作用。该研究通过体内外实验和一系列机制研究，证明了GLP-1受体激动剂通过去乙酰化酶SIRT1介导减少热休克因子1（HSF1）的乙酰化水平，从而上调热休克蛋白（HSPs）的表达，最终改善脂毒性所致肝脏内质网应激及脂质沉积。研究结果揭示了GLP-1受体激动剂调控脂肪肝状态时肝脏内质网应激的新机制，为临床上使用GLP-1受体激动剂治疗2型糖尿病或肥胖相关的脂肪肝提供了理论依据，同时也为脂肪肝防治药物的开发提供了新的靶点。

本研究得到了国家自然科学基金中加合作项目（81261120565）、***和创新团队项目（82000-18811100）、国家自然科学基金青年基金和面上项目（81300705、81670782）的资助。

原始出处：

Zheng X，et al.，SIRT1/HSF1/HSP pathway is essential for exenatide-alleviated， lipid-induced hepatic endoplasmic reticulum stress.Hepatology. 2017 Sep；66(3)：809-824.

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2017-12-23 plovem1008

随着对GLP-1受体激动剂不同器官影响机制的深入研究.定会开启更加神秘的医学大门

85 0
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2017-12-22 Eleven11

#GLP-1受体激动剂#

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2017-12-22 yibei

#GLP-1#

33 0
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2017-12-22 gwc384

#EPA#

31 0
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2017-12-22 医者仁心

#应激#

30 0
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2017-12-22 medscijoin

#激动剂#

27 0
[GetPortalCommentsPageByObjectIdResponse(id=271938, encodeId=bb142e19381e, content=随着对GLP-1受体激动剂不同器官影响机制的深入研究.定会开启更加神秘的医学大门, beContent=null, objectType=article, channel=null, level=null, likeNumber=85, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTJDp4Z8xRnF5xoAvxFib37blBtqjBiatyDQVlNlbycPZan1uy7Wdzmznkaian7cqnIhiawa5qIJjMMFBg/0, createdBy=af6f1446386, createdName=plovem1008, createdTime=Sat Dec 23 21:45:24 CST 2017, time=2017-12-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1294024, encodeId=0ec912940245d, content=<a href='/topic/show?id=bb0e8081b2' target=_blank style='color:#2F92EE;'>#GLP-1受体激动剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8081, encryptionId=bb0e8081b2, topicName=GLP-1受体激动剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e183245, createdName=Eleven11, createdTime=Fri Dec 22 10:55:00 CST 2017, time=2017-12-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1422714, encodeId=fa151422e1446, content=<a href='/topic/show?id=54fa80e701' target=_blank style='color:#2F92EE;'>#GLP-1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8077, encryptionId=54fa80e701, topicName=GLP-1)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f8f23732777, createdName=yibei, createdTime=Fri Dec 22 10:55:00 CST 2017, time=2017-12-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1426956, encodeId=f6da1426956d8, content=<a href='/topic/show?id=221d685172' target=_blank style='color:#2F92EE;'>#EPA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6851, encryptionId=221d685172, topicName=EPA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=4a9b4077760, createdName=gwc384, createdTime=Fri Dec 22 10:55:00 CST 2017, time=2017-12-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1445192, encodeId=056c144519299, content=<a href='/topic/show?id=61e74928629' target=_blank style='color:#2F92EE;'>#应激#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=49286, encryptionId=61e74928629, topicName=应激)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=医者仁心, createdTime=Fri Dec 22 10:55:00 CST 2017, time=2017-12-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1627754, encodeId=8eea162e75485, content=<a href='/topic/show?id=ab4f66e8913' target=_blank style='color:#2F92EE;'>#激动剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=66789, encryptionId=ab4f66e8913, topicName=激动剂)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=95bc21134754, createdName=medscijoin, createdTime=Fri Dec 22 10:55:00 CST 2017, time=2017-12-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=270983, encodeId=afee2e09837b, content=学习了.谢谢., beContent=null, objectType=article, channel=null, level=null, likeNumber=78, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/xkvRjYnJzzRJ2R0y7VhicibvkjPWHjIMmu4ZpKnE9cWAu4lVicS3uDUCfF4M4JWvrkrYfpb2KehPV0Ee29tPqyPEebBUibiaKhnvD/0, createdBy=f8412001184, createdName=惠映实验室, createdTime=Wed Dec 20 20:34:10 CST 2017, time=2017-12-20, status=1, ipAttribution=)]
2017-12-20 惠映实验室

学习了.谢谢.

78 0

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Hepatology：GLP-1受体激动剂改善脂肪肝时肝脏内质网应激新机制

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