Diabetologia：小鼠中LIGHT（TNFSF14）细胞因子的基因失活可恢复葡萄糖稳态并减少肝脂肪变性

2019-12-24 MedSci MedSci原创

一般来说，非酒精性脂肪肝疾病（<span lang="EN-US" style="font-size:12.0pt;mso-bidi-font-size:14.0pt;font-family:"Calibri","sans-serif"; mso-fareast-font-family:宋体;mso-bidi-font-family:"Times

一般来说，非酒精性脂肪肝疾病（NAFLD）与2型糖尿病有关。除其他外，NAFLD的进展是通过激活炎症途径来介导的。在本研究中，在缺乏细胞因子的小鼠中探讨了促炎细胞因子LIGHT（TNFSF14）在NAFLD和2型糖尿病中的作用。

LIGHT（Light-/-）小鼠和WT对照接受常规饮食（RCD）或高脂高胆固醇饮食（HFHCD），并持续16周在两种饮食方案中都研究了LIGHT及其受体，疱疹病毒进入介质（HVEM）和淋巴毒素β受体（LTβR）的表达。在接受RCD和HFHCD喂养的Light-/-和WT小鼠中探索了葡萄糖耐量，胰岛素敏感性，非酒精性脂肪肝（NAFL），全身和组织炎症以及代谢基因表达。还对胰岛素信号受损的HFHCD喂养的Irs2 +/-小鼠的肝组织和炎症评估了LIGHT缺乏的影响。

在以RCD喂养的WT小鼠中，LIGHT缺乏对NAFL或组织和全身炎症的代谢没有影响。与由RCD喂养的WT对照相比，由HFHCD喂养的WT小鼠的肝脏中HVEM和LTβR显着增加。在HFHCD下的WT小鼠中，LIGHT缺乏改善了葡萄糖耐量和胰岛素敏感性。与由HFHCD喂养的WT对照相比，以HFHCD喂养的Light-/-小鼠的非酒精性脂肪肝疾病活动（NAS）评分，肝CD3 + T淋巴细胞和F4 / 80 +巨噬细胞减少。与脂肪组织在肝稳态中的潜在作用一致，Light-/-小鼠表现出增强的抗炎性F4 / 80 + CD206 +脂肪组织巨噬细胞和减少的促炎性F4 / 80 + CD11c +脂肪组织巨噬细胞。此外，来自Light-/-小鼠的脂肪组织外植体显示出单核细胞趋化蛋白1（MCP1），TNF-α和IL-17细胞因子的分泌减少。循环中的轻型白细胞始终显示出巡逻的Ly6Clow单核细胞水平升高，Th9 T细胞亚群降低，血浆TNF-α和IL-6水平降低。同样，Irs2 +/-小鼠的LIGHT缺乏表现出胰岛素信号受损，也减少了NAFL以及全身和脂肪组织的炎症。对Light-/-小鼠肝脏中肝基因表达的分析显示Zbtb16水平降低，Zbtb16水平是自然杀伤性T（NKT）细胞功能所必需的转录因子，还有两个与NAFLD和纤维化相关的基因Klf6和Tlr4。

这些结果表明，HFHCD中的LIGHT缺乏改善了肝糖耐量，并减少了肝炎和NAFL。这伴随着全身炎症的减少和脂肪组织细胞因子的分泌减少以及与NAFLD有关的关键基因如Klf6和Tlr4的表达变化。这些结果表明，阻断LIGHT依赖信号的治疗可能有助于恢复肝内稳态和抑制NAFLD。

原始出处：

Andrea Herrero-Cervera，Ángela Vinué，Genetic inactivation of the LIGHT (TNFSF14) cytokine in mice restores glucose homeostasis and diminishes hepatic steatosis

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2020-07-21 ms9608593228839890

#DIA#

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2020-02-17 10518105zz

#肝脂肪变#

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createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83eqjVbfRD4f4vibEcZVcvato8Qib1gGtZJiayXCMFgHrkeErSiaxdYMiabKGxY2an9muxWCkUJbjFPViaC6A/132, createdBy=e4fb2361580, createdName=snowpeakxu, createdTime=Thu Dec 26 04:31:00 CST 2019, time=2019-12-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1463699, encodeId=49eb1463699b0, content=<a href='/topic/show?id=7d27381288e' target=_blank style='color:#2F92EE;'>#变性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=94, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=38128, encryptionId=7d27381288e, topicName=变性)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f69f6545041, createdName=huangdf, createdTime=Thu Dec 26 04:31:00 CST 2019, time=2019-12-26, status=1, ipAttribution=)]
2020-06-16 wgsun

#脂肪变性#

116 0
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createdBy=531535069436, createdName=10518105zz, createdTime=Mon Feb 17 18:31:00 CST 2020, time=2020-02-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1948788, encodeId=ae141948e88c7, content=<a href='/topic/show?id=0602843360f' target=_blank style='color:#2F92EE;'>#脂肪变性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=116, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=84336, encryptionId=0602843360f, topicName=脂肪变性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=346311, createdName=wgsun, createdTime=Tue Jun 16 13:31:00 CST 2020, time=2020-06-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1761266, encodeId=fd011e6126629, content=<a href='/topic/show?id=9bea33520d' target=_blank style='color:#2F92EE;'>#BET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3352, encryptionId=9bea33520d, topicName=BET)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9a1a37427546, createdName=ms5439512287675881, createdTime=Sat Oct 31 20:31:00 CST 2020, time=2020-10-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1676086, encodeId=578716e60868e, content=<a href='/topic/show?id=a44f8825899' target=_blank style='color:#2F92EE;'>#葡萄糖稳态#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=88258, encryptionId=a44f8825899, topicName=葡萄糖稳态)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=37f027318242, createdName=医生2403, createdTime=Mon Mar 09 16:31:00 CST 2020, time=2020-03-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1809603, encodeId=c492180960303, content=<a href='/topic/show?id=6cd683e603b' target=_blank style='color:#2F92EE;'>#胞因子#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=60, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=83760, encryptionId=6cd683e603b, topicName=胞因子)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdqq.qlogo.cn/qqapp/101296147/017ED6AFEB45F49165298113DDC0656A/100, createdBy=84182500174, createdName=ms7019579240139182, createdTime=Sun Apr 12 04:31:00 CST 2020, time=2020-04-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1646744, encodeId=9c3b1646e4402, content=<a href='/topic/show?id=4478e5315e1' target=_blank style='color:#2F92EE;'>#稳态#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=98, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=75315, encryptionId=4478e5315e1, topicName=稳态)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=3ebc23344390, createdName=changfy, createdTime=Tue Dec 01 19:31:00 CST 2020, time=2020-12-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1283637, encodeId=0a03128363e24, content=<a href='/topic/show?id=2c00e784416' target=_blank style='color:#2F92EE;'>#细胞因子#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=53, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77844, encryptionId=2c00e784416, topicName=细胞因子)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=0ad8182, createdName=axin009, createdTime=Thu Dec 26 04:31:00 CST 2019, time=2019-12-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1401750, encodeId=fcba1401e508a, content=<a href='/topic/show?id=17e21e57943' target=_blank style='color:#2F92EE;'>#TNF#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=137, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17579, encryptionId=17e21e57943, topicName=TNF)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83eqjVbfRD4f4vibEcZVcvato8Qib1gGtZJiayXCMFgHrkeErSiaxdYMiabKGxY2an9muxWCkUJbjFPViaC6A/132, createdBy=e4fb2361580, createdName=snowpeakxu, createdTime=Thu Dec 26 04:31:00 CST 2019, time=2019-12-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1463699, encodeId=49eb1463699b0, content=<a href='/topic/show?id=7d27381288e' target=_blank style='color:#2F92EE;'>#变性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=94, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=38128, encryptionId=7d27381288e, topicName=变性)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f69f6545041, createdName=huangdf, createdTime=Thu Dec 26 04:31:00 CST 2019, time=2019-12-26, status=1, ipAttribution=)]
2020-10-31 ms5439512287675881

#BET#

70 0
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encryptionId=9bea33520d, topicName=BET)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9a1a37427546, createdName=ms5439512287675881, createdTime=Sat Oct 31 20:31:00 CST 2020, time=2020-10-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1676086, encodeId=578716e60868e, content=<a href='/topic/show?id=a44f8825899' target=_blank style='color:#2F92EE;'>#葡萄糖稳态#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=88258, encryptionId=a44f8825899, topicName=葡萄糖稳态)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=37f027318242, createdName=医生2403, createdTime=Mon Mar 09 16:31:00 CST 2020, time=2020-03-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1809603, encodeId=c492180960303, content=<a href='/topic/show?id=6cd683e603b' target=_blank style='color:#2F92EE;'>#胞因子#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=60, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=83760, encryptionId=6cd683e603b, topicName=胞因子)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdqq.qlogo.cn/qqapp/101296147/017ED6AFEB45F49165298113DDC0656A/100, createdBy=84182500174, createdName=ms7019579240139182, createdTime=Sun Apr 12 04:31:00 CST 2020, time=2020-04-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1646744, encodeId=9c3b1646e4402, content=<a href='/topic/show?id=4478e5315e1' target=_blank style='color:#2F92EE;'>#稳态#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=98, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=75315, encryptionId=4478e5315e1, topicName=稳态)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=3ebc23344390, createdName=changfy, createdTime=Tue Dec 01 19:31:00 CST 2020, time=2020-12-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1283637, encodeId=0a03128363e24, content=<a href='/topic/show?id=2c00e784416' target=_blank style='color:#2F92EE;'>#细胞因子#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=53, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77844, encryptionId=2c00e784416, topicName=细胞因子)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=0ad8182, createdName=axin009, createdTime=Thu Dec 26 04:31:00 CST 2019, time=2019-12-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1401750, encodeId=fcba1401e508a, content=<a href='/topic/show?id=17e21e57943' target=_blank style='color:#2F92EE;'>#TNF#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=137, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17579, encryptionId=17e21e57943, topicName=TNF)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83eqjVbfRD4f4vibEcZVcvato8Qib1gGtZJiayXCMFgHrkeErSiaxdYMiabKGxY2an9muxWCkUJbjFPViaC6A/132, createdBy=e4fb2361580, createdName=snowpeakxu, createdTime=Thu Dec 26 04:31:00 CST 2019, time=2019-12-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1463699, encodeId=49eb1463699b0, content=<a href='/topic/show?id=7d27381288e' target=_blank style='color:#2F92EE;'>#变性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=94, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=38128, encryptionId=7d27381288e, topicName=变性)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f69f6545041, createdName=huangdf, createdTime=Thu Dec 26 04:31:00 CST 2019, time=2019-12-26, status=1, ipAttribution=)]
2020-03-09 医生2403

#葡萄糖稳态#

79 0
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encryptionId=9bea33520d, topicName=BET)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9a1a37427546, createdName=ms5439512287675881, createdTime=Sat Oct 31 20:31:00 CST 2020, time=2020-10-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1676086, encodeId=578716e60868e, content=<a href='/topic/show?id=a44f8825899' target=_blank style='color:#2F92EE;'>#葡萄糖稳态#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=88258, encryptionId=a44f8825899, topicName=葡萄糖稳态)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=37f027318242, createdName=医生2403, createdTime=Mon Mar 09 16:31:00 CST 2020, time=2020-03-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1809603, encodeId=c492180960303, content=<a href='/topic/show?id=6cd683e603b' target=_blank style='color:#2F92EE;'>#胞因子#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=60, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=83760, encryptionId=6cd683e603b, topicName=胞因子)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdqq.qlogo.cn/qqapp/101296147/017ED6AFEB45F49165298113DDC0656A/100, createdBy=84182500174, createdName=ms7019579240139182, createdTime=Sun Apr 12 04:31:00 CST 2020, time=2020-04-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1646744, encodeId=9c3b1646e4402, content=<a href='/topic/show?id=4478e5315e1' target=_blank style='color:#2F92EE;'>#稳态#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=98, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=75315, encryptionId=4478e5315e1, topicName=稳态)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=3ebc23344390, createdName=changfy, createdTime=Tue Dec 01 19:31:00 CST 2020, time=2020-12-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1283637, encodeId=0a03128363e24, content=<a href='/topic/show?id=2c00e784416' target=_blank style='color:#2F92EE;'>#细胞因子#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=53, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77844, encryptionId=2c00e784416, topicName=细胞因子)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=0ad8182, createdName=axin009, createdTime=Thu Dec 26 04:31:00 CST 2019, time=2019-12-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1401750, encodeId=fcba1401e508a, content=<a href='/topic/show?id=17e21e57943' target=_blank style='color:#2F92EE;'>#TNF#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=137, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17579, encryptionId=17e21e57943, topicName=TNF)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83eqjVbfRD4f4vibEcZVcvato8Qib1gGtZJiayXCMFgHrkeErSiaxdYMiabKGxY2an9muxWCkUJbjFPViaC6A/132, createdBy=e4fb2361580, createdName=snowpeakxu, createdTime=Thu Dec 26 04:31:00 CST 2019, time=2019-12-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1463699, encodeId=49eb1463699b0, content=<a href='/topic/show?id=7d27381288e' target=_blank style='color:#2F92EE;'>#变性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=94, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=38128, encryptionId=7d27381288e, topicName=变性)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f69f6545041, createdName=huangdf, createdTime=Thu Dec 26 04:31:00 CST 2019, time=2019-12-26, status=1, ipAttribution=)]
2020-04-12 ms7019579240139182

#胞因子#

60 0
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2020-12-01 changfy

#稳态#

98 0
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2019-12-26 axin009

#细胞因子#

53 0
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2019-12-26 snowpeakxu

#TNF#

137 0
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ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1283637, encodeId=0a03128363e24, content=<a href='/topic/show?id=2c00e784416' target=_blank style='color:#2F92EE;'>#细胞因子#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=53, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77844, encryptionId=2c00e784416, topicName=细胞因子)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=0ad8182, createdName=axin009, createdTime=Thu Dec 26 04:31:00 CST 2019, time=2019-12-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1401750, encodeId=fcba1401e508a, content=<a href='/topic/show?id=17e21e57943' target=_blank style='color:#2F92EE;'>#TNF#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=137, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17579, encryptionId=17e21e57943, topicName=TNF)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83eqjVbfRD4f4vibEcZVcvato8Qib1gGtZJiayXCMFgHrkeErSiaxdYMiabKGxY2an9muxWCkUJbjFPViaC6A/132, createdBy=e4fb2361580, createdName=snowpeakxu, createdTime=Thu Dec 26 04:31:00 CST 2019, time=2019-12-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1463699, encodeId=49eb1463699b0, content=<a href='/topic/show?id=7d27381288e' target=_blank style='color:#2F92EE;'>#变性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=94, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=38128, encryptionId=7d27381288e, topicName=变性)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f69f6545041, createdName=huangdf, createdTime=Thu Dec 26 04:31:00 CST 2019, time=2019-12-26, status=1, ipAttribution=)]
2019-12-26 huangdf

#变性#

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Diabetologia：小鼠中LIGHT（TNFSF14）细胞因子的基因失活可恢复葡萄糖稳态并减少肝脂肪变性

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