JCI:无需节食和运动!“PDE5抑制剂的表哥”能够刺激脂肪燃烧,促进减肥

2021-10-11 “生物世界”公众号 “生物世界”公众号

肥胖是世界卫生组织确定的十大慢性疾病之一,全世界有19亿成年人超重,6亿人肥胖。在中国,超重和肥胖人群已逾3亿人。因此,肥胖及其相关疾病是全球主要健康问题,其发病率日益令人担忧。

肥胖是世界卫生组织确定的十大慢性疾病之一,全世界有19亿成年人超重,6亿人肥胖。在中国,超重和肥胖人群已逾3亿人。因此,肥胖及其相关疾病是全球主要健康问题,其发病率日益令人担忧。

肥胖既是一种特征,也是一种疾病,肥胖者更有可能患上糖尿病、心血管疾病和慢性肾脏病等。

2021年10月7日, 约翰·霍普金斯大学的研究人员在 Journal of Clinical Investigation 期刊上发表了题为:Inhibition of phosphodiesterase type 9 reduces obesity and cardiometabolic syndrome in mice 的研究论文。

该研究发现一种无需控制饮食和日常活动的药物,该药物通过刺激细胞燃烧更多脂肪,促进减肥。在小鼠模型中发现,药物可以减少小鼠的肥胖和脂肪肝,并改善它们的心脏功能。

早期的研究表明,PDE9 酶存在于心脏中,并导致由高血压引发的心脏病,阻断 PDE9 会增加一种称为环 GMP 的小分子的数量,进而控制全身细胞功能。PDE9 是另一种称为 PDE5 的蛋白酶的表亲,西地那非(俗称伟哥)正是 PDE5 的抑制剂。而 PDE9 抑制剂是实验性的,尚无药物名称,因此也被称为“伟哥的表哥”。

基于这些结果,研究人员怀疑 PDE9 抑制剂可能会改善心脏代谢综合征,包括高血压、高血糖、胆固醇和甘油三酯、肥胖等。

为了测试 PDE9 抑制剂对肥胖和心脏代谢综合征的影响,研究人员让小鼠进行高脂肪饮食,四个月后小鼠体重翻倍,血脂高和糖尿病。一组雌性小鼠通过手术切除了卵巢,还对大多数小鼠心脏施加了压力,以更好地模拟心脏代谢综合征。

在接下来的六到八周内,分别喂食小鼠口服 PDE9 抑制剂或安慰剂。实验期内,小鼠每天的食物消耗量或体力活动也没有改变。

在为期8周的药物试验期间,服用安慰剂的小鼠体重平均增加22%,而服用 PDE9 抑制剂的小鼠体重下降了5.6%。MRI身体成分分析发现,PDE9 治疗可减少总脂肪量,且保持肌肉体重不变。

服用 PDE9 抑制剂的小鼠体重下降,且减少的是脂肪

此外,与安慰剂相比,在 PDE9 抑制剂组中,血液胆固醇和甘油三酯降低了,并将肝脏中的脂肪降低到正常饮食小鼠的水平,心脏也得到改善。

进一步分析发现,PDE9 抑制通过激活脂肪代谢主调节器(PPARa)来产生这些效果。通过刺激 PPARa,控制脂肪摄入细胞及其作为燃料的蛋白质的基因水平广泛增加。当 PPARa 在细胞或机体中被阻断时,PDE9 抑制对肥胖和脂肪燃烧的影响也消失了。

不仅如此,研究人员还发现雌激素通常在女性的脂肪调节中发挥 PPARa 的这种作用,但是当它的水平像绝经后一样下降时,PPARa 对调节脂肪变得更加重要,因此抑制 PDE9 的作用更大。

在有卵巢的雌性小鼠中,没有发现类似益处。研究人员指出,这是由于雌激素已经达到了抑制 PDE9 刺激脂肪燃烧的作用。

研究人员指出,如果实验结果发现适用于人类,体重250磅的人在不改变饮食或运动习惯的情况下,口服 PDE9 抑制剂可以减掉50磅左右。

原始出处:

Sumita Mishra, et al. Inhibition of phosphodiesterase type 9 reduces obesity and cardiometabolic syndrome in mice. JCI, 2021.

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    2021-10-12 lsndxfj
  6. [GetPortalCommentsPageByObjectIdResponse(id=1852775, encodeId=1a9c1852e75eb, content=<a href='/topic/show?id=f0a254918f0' target=_blank style='color:#2F92EE;'>#抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=54918, encryptionId=f0a254918f0, topicName=抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=44a360, createdName=jklm09, createdTime=Wed Jul 27 19:01:59 CST 2022, time=2022-07-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1950493, encodeId=062819504935d, content=<a href='/topic/show?id=6f8184365e1' target=_blank style='color:#2F92EE;'>#脂肪燃烧#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=84365, encryptionId=6f8184365e1, topicName=脂肪燃烧)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f503121, createdName=zjubiostat, createdTime=Mon Aug 01 19:01:59 CST 2022, time=2022-08-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1982136, encodeId=96ad19821367e, content=<a href='/topic/show?id=12c010266f0' target=_blank style='color:#2F92EE;'>#JCI#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10266, encryptionId=12c010266f0, topicName=JCI)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5e30378, createdName=caobinglei8079, createdTime=Fri Aug 19 23:01:59 CST 2022, time=2022-08-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1984888, encodeId=2913198488821, content=<a href='/topic/show?id=b9e21394eba' target=_blank style='color:#2F92EE;'>#PDE5抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13947, encryptionId=b9e21394eba, topicName=PDE5抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/lGEyfsKnIkkH93xUPMrUUycLh2XOfJJsphwPsVqDx8somSOepIFy9QE0MVAwDW3AS7V1epJ4tbPL9ADJLicvm8A/132, createdBy=b5132500067, createdName=ms55066533437992, createdTime=Wed Apr 06 00:01:59 CST 2022, time=2022-04-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1414151, encodeId=fe80141415155, content=<a href='/topic/show?id=e215868e93c' target=_blank style='color:#2F92EE;'>#节食#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=86879, encryptionId=e215868e93c, topicName=节食)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=da0d3042812, createdName=lsndxfj, createdTime=Tue Oct 12 11:01:59 CST 2021, time=2021-10-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1059662, encodeId=df551059662fc, content=光谈疗效,不说副作用, beContent=null, objectType=article, channel=null, level=null, likeNumber=67, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=2f255526204, createdName=我思故我在2, createdTime=Tue Oct 12 08:55:24 CST 2021, time=2021-10-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1059495, encodeId=3f511059495dc, content=估计副作用不小吧, beContent=null, objectType=article, channel=null, level=null, likeNumber=61, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20211011/8ae533557e62460894b9050a9547436e/aa7e036105e9473e9a0569e5a0046806.jpg, createdBy=e2465631665, createdName=心外人, createdTime=Mon Oct 11 15:52:21 CST 2021, time=2021-10-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1245256, encodeId=d2cb1245256dd, content=什么时候有懒人用的减肥神药?, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=CHANGE, createdTime=Sun Oct 10 23:01:59 CST 2021, time=2021-10-10, status=1, ipAttribution=)]
    2021-10-12 我思故我在2

    光谈疗效,不说副作用

    0

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    2021-10-11 心外人

    估计副作用不小吧

    0

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    2021-10-10 CHANGE

    什么时候有懒人用的减肥神药?

    0

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