Science:流的不是汗,是脂肪!细胞因子治疗的小鼠通过“出汗”脂肪减轻了体重!

2021-07-30 MedSci原创 MedSci原创

肥胖及其相关并发症是严重的全球问题。尽管公共卫生举措不断增加,肥胖率仍在继续上升。因此,迫切需要确定影响肥胖的途径。

肥胖及其相关并发症是严重的全球问题。尽管公共卫生举措不断增加,肥胖率仍在继续上升。因此,迫切需要确定影响肥胖的途径。

 之前的一些研究表明,免疫系统可以调节脂肪组织及其代谢功能。2 型免疫细胞,例如 2 型先天淋巴细胞 (ILC2) 和嗜酸性粒细胞,可提高代谢率,而调节性 T 细胞(T reg细胞)可促进胰岛素敏感性。那通过调节 T 细胞能不能减轻体重呢

20217月30号一项发表在科学》杂志上一项新研究发现与对照组相比,用称为 TSLP 的细胞因子治疗肥胖小鼠会导致显着的腹部脂肪和体重减轻。出乎意料的是,脂肪减少与食物摄入量减少或新陈代谢加快无关。相反,研究人员发现 TSLP 刺激免疫系统,诱导传统 T 细胞迁移到皮肤中的皮脂腺,通过皮肤的产油皮脂腺释放脂质。研究员证明了可以通过以富含能量的皮脂的形式从皮肤分泌卡路里来减少脂肪。

皮脂是一种富含脂质的物质,可增强皮肤的屏障功能。这种机制可能进化为增强皮肤抗微生物防御能力,可能成为未来肥胖症治疗的目标。

胸腺基质淋巴细胞生成素 (TSLP) 是一种细胞因子——一种免疫系统蛋白——。Kambayashi 研究小组一直在研究这种细胞因子在激活 2 型免疫细胞和扩展 T 调节细胞方面的扩展作用。由于过去的研究表明这些细胞可以调节能量代谢,研究人员预测用 TSLP 治疗超重小鼠可以刺激免疫反应,从而可以抵消肥胖的一些有害影响。

为了测试 TSLP 对 2 型糖尿病的影响,研究人员向肥胖小鼠注射了一种病毒载体,这种病毒载体会增加它们身体的 TSLP 水平。

四个星期后,研究小组发现 TSLP 不仅影响了他们的糖尿病风险,而且实际上逆转了小鼠的肥胖症,这些小鼠被喂以高脂肪饮食。虽然对照组体重继续增加,但接受 TSLP 治疗的小鼠的体重平均在 28 天内从 45 克下降到健康的 25 克。

最引人注目的是,TSLP 治疗的小鼠也减少了它们的内脏脂肪量。内脏脂肪是储存在腹部主要器官周围的白色脂肪,会增加糖尿病、心脏病和中风的风险。这些小鼠的血糖和空腹胰岛素水平也有所改善,脂肪肝疾病的风险也有所降低。

鉴于戏剧性的结果,Kambayashi 假设 TSLP 使小鼠感到恶心并降低了它们的食欲。然而,经过进一步测试,他的团队发现,与未接受治疗的小鼠相比,接受 TSLP 治疗的小鼠实际上多吃 20% 至 30%,能量消耗、基础代谢率和活动水平相似。

 为了解释体重减轻,Kambayashi 回忆了他之前忽略的一个小观察:“当我观察接受 TSLP 治疗的小鼠的皮毛时,我注意到它们在光线下闪闪发光。我总是确切地知道哪些小鼠接受了治疗,因为他们比其他人更闪亮,”他说。

Kambayashi 认为这是一个牵强附会的想法——它们油腻的头发是否表明老鼠正在“出汗”皮肤上的脂肪?

为了验证这一理论,研究人员对接受 TSLP 治疗的小鼠和对照组进行剃毛,然后从它们的皮毛中提取油脂。他们发现 Kambayashi 的假设是正确的:闪亮的皮毛含有皮脂特异性脂质。

TSLP 激活 T 细胞以促进皮脂分泌

通过 TSLP 受体 (TSLPR) 对 T 细胞的非抗原依赖性刺激诱导它们迁移到皮肤 SGs 并促进皮脂分泌和 AMP 表达。TSLP 过度表达导致循环脂质向皮肤明显转移,从而降低脂肪组织和肝脏中的脂质含量。在基线时,TSLP 刺激的 T 细胞通过 SGs 维持皮肤屏障功能。VLDL,极低密度脂蛋白

皮脂是一种由皮脂腺中的皮脂细胞(高度特化的上皮细胞)产生的高热量物质,有助于形成皮肤屏障。这证实了通过皮肤释放油脂是 TSLP 诱导的脂肪减少的原因。

为了检查 TSLP 是否可能在控制人类油脂分泌方面发挥作用,研究人员随后在公开数据集中检查了 TSLP 和一组 18 个皮脂腺相关基因。这表明 TSLP 表达与健康人皮肤中的皮脂腺基因表达显着正相关。研究作者写道,在人类中,将皮脂释放转移到“高速”可能会导致“脂肪出汗”和体重减轻。

的研究结果支持一个模型,其中 TSLP 过表达通过诱导皮肤 T 细胞迁移和增加皮脂分泌过多而导致 WAT 损失。此外,TSLP 和 T 细胞稳态调节皮脂生成和皮肤 AMP 表达,突出了适应性免疫系统在维持皮肤屏障功能方面的意想不到的作用。

 

参考文献 Thymic stromal lymphopoietin induces adipose loss through sebum hypersecretion, Science (2021). DOI: 10.1126/science.abd2893

 

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beContent=null, objectType=article, channel=null, level=null, likeNumber=94, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210218/994a038e370045d8944a573fa77e3034/3cf31c7b86844fbc9b4b755e348eb533.jpg, createdBy=3af25452664, createdName=马群耀是理想型, createdTime=Sat Jul 31 00:28:47 CST 2021, time=2021-07-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1003917, encodeId=262c100391ef1, content=好文章,谢谢分享。, beContent=null, objectType=article, channel=null, level=null, likeNumber=80, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTJlfgys76DEiaNtbYo2re3ibjrUPTRibEXRyFwAB4aAGiave842S0FQDf0wAoaH226NiaSoPPDzhndsf1g/132, createdBy=88b489038, createdName=yangchou, createdTime=Fri Jul 30 16:11:34 CST 2021, time=2021-07-30, status=1, ipAttribution=), 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    2021-10-05 小小的丁香花

    很有意思😄

    0

  4. 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    2021-09-14 124902dfm95暂无昵称

    很神奇,也有探索价值

    0

  5. 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  6. 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    2021-07-31 jichang
  7. [GetPortalCommentsPageByObjectIdResponse(id=1809644, encodeId=aa801809644fd, 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=43, 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=Wed Mar 23 00:25:57 CST 2022, time=2022-03-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1804993, encodeId=67631804993ae, content=<a href='/topic/show?id=0637e78490c' target=_blank style='color:#2F92EE;'>#细胞因子治疗#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77849, encryptionId=0637e78490c, topicName=细胞因子治疗)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d4b7363, createdName=pandamao2010, createdTime=Sat Oct 02 14:25:57 CST 2021, time=2021-10-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1057741, encodeId=4bdb105e74105, content=很有意思😄, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210804/5785b262ac614e2787c8b09e8d8ae840/5cf1162cd10d42bc817ae4b32662d7f8.jpg, createdBy=c27d4938136, createdName=小小的丁香花, createdTime=Tue Oct 05 07:08:51 CST 2021, time=2021-10-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1050155, encodeId=9ec7105015593, content=很神奇,也有探索价值, beContent=null, objectType=article, channel=null, level=null, likeNumber=102, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, 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beContent=null, objectType=article, channel=null, level=null, likeNumber=94, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210218/994a038e370045d8944a573fa77e3034/3cf31c7b86844fbc9b4b755e348eb533.jpg, createdBy=3af25452664, createdName=马群耀是理想型, createdTime=Sat Jul 31 00:28:47 CST 2021, time=2021-07-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1003917, encodeId=262c100391ef1, content=好文章,谢谢分享。, beContent=null, objectType=article, channel=null, level=null, likeNumber=80, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTJlfgys76DEiaNtbYo2re3ibjrUPTRibEXRyFwAB4aAGiave842S0FQDf0wAoaH226NiaSoPPDzhndsf1g/132, createdBy=88b489038, createdName=yangchou, createdTime=Fri Jul 30 16:11:34 CST 2021, time=2021-07-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1003774, encodeId=2d411003e7459, content=减肥的希望, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b7a31928393, createdName=学医无涯, createdTime=Fri Jul 30 07:31:09 CST 2021, time=2021-07-30, status=1, ipAttribution=)]
    2021-07-31 FukaiBao
  8. [GetPortalCommentsPageByObjectIdResponse(id=1809644, encodeId=aa801809644fd, 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=43, 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=Wed Mar 23 00:25:57 CST 2022, time=2022-03-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1804993, encodeId=67631804993ae, content=<a href='/topic/show?id=0637e78490c' target=_blank style='color:#2F92EE;'>#细胞因子治疗#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77849, encryptionId=0637e78490c, 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channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15998, encryptionId=2949159989d, topicName=SCIE)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=17a3387, createdName=jichang, createdTime=Sat Jul 31 22:25:57 CST 2021, time=2021-07-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1564195, encodeId=1af4156419586, content=<a href='/topic/show?id=01ae314135d' target=_blank style='color:#2F92EE;'>#出汗#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=31413, encryptionId=01ae314135d, topicName=出汗)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8adc15291882, createdName=FukaiBao, createdTime=Sat Jul 31 22:25:57 CST 2021, time=2021-07-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1004131, encodeId=ed581004131ac, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=94, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210218/994a038e370045d8944a573fa77e3034/3cf31c7b86844fbc9b4b755e348eb533.jpg, createdBy=3af25452664, createdName=马群耀是理想型, createdTime=Sat Jul 31 00:28:47 CST 2021, time=2021-07-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1003917, encodeId=262c100391ef1, content=好文章,谢谢分享。, beContent=null, objectType=article, channel=null, level=null, likeNumber=80, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTJlfgys76DEiaNtbYo2re3ibjrUPTRibEXRyFwAB4aAGiave842S0FQDf0wAoaH226NiaSoPPDzhndsf1g/132, createdBy=88b489038, createdName=yangchou, createdTime=Fri Jul 30 16:11:34 CST 2021, time=2021-07-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1003774, encodeId=2d411003e7459, content=减肥的希望, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b7a31928393, createdName=学医无涯, createdTime=Fri Jul 30 07:31:09 CST 2021, time=2021-07-30, status=1, ipAttribution=)]
    2021-07-31 马群耀是理想型

    学习了

    0

  9. 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channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15998, encryptionId=2949159989d, topicName=SCIE)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=17a3387, createdName=jichang, createdTime=Sat Jul 31 22:25:57 CST 2021, time=2021-07-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1564195, encodeId=1af4156419586, content=<a href='/topic/show?id=01ae314135d' target=_blank style='color:#2F92EE;'>#出汗#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=31413, encryptionId=01ae314135d, topicName=出汗)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8adc15291882, createdName=FukaiBao, createdTime=Sat Jul 31 22:25:57 CST 2021, time=2021-07-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1004131, encodeId=ed581004131ac, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=94, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210218/994a038e370045d8944a573fa77e3034/3cf31c7b86844fbc9b4b755e348eb533.jpg, createdBy=3af25452664, createdName=马群耀是理想型, createdTime=Sat Jul 31 00:28:47 CST 2021, time=2021-07-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1003917, encodeId=262c100391ef1, content=好文章,谢谢分享。, beContent=null, objectType=article, channel=null, level=null, likeNumber=80, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTJlfgys76DEiaNtbYo2re3ibjrUPTRibEXRyFwAB4aAGiave842S0FQDf0wAoaH226NiaSoPPDzhndsf1g/132, createdBy=88b489038, createdName=yangchou, createdTime=Fri Jul 30 16:11:34 CST 2021, time=2021-07-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1003774, encodeId=2d411003e7459, content=减肥的希望, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b7a31928393, createdName=学医无涯, createdTime=Fri Jul 30 07:31:09 CST 2021, time=2021-07-30, status=1, ipAttribution=)]
    2021-07-30 yangchou

    好文章,谢谢分享。

    0

  10. 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    2021-07-30 学医无涯

    减肥的希望

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