Nat Metab :生酮饮食或可预防甚至逆转心力衰竭

2020-11-05 探索菌 生物探索

一直以来,科学家们都在尝试通过改变饮食方式帮助人们改善健康状况。其中,高脂、低碳水化合物和适当蛋白质的生酮饮食方式颇受大众追捧,不仅在减肥方面效果显着,而且早前已被证明能够有效治疗癫痫。

一直以来,科学家们都在尝试通过改变饮食方式帮助人们改善健康状况。其中,高脂、低碳水化合物和适当蛋白质的生酮饮食方式颇受大众追捧,不仅在减肥方面效果显着,而且早前已被证明能够有效治疗癫痫。然而,生酮饮食的妙用似乎远远不止于此。

《Nature Metabolism》发布了两篇与生酮饮食和心脏衰竭有关的文章,分别是美国圣路易斯大学的研究人员带来的“Nutritional modulation of heart failure in mitochondrial pyruvate carrier–deficient mice”以及爱荷华大学卡佛医学院的研究人员带来的“Mitochondrial pyruvate carriers are required for myocardial stress adaptation”。

两篇文章均指出,高脂或生酮饮食在小鼠实验中可以完全预防甚至逆转由代谢过程引起的心力衰竭。

心脏是一个具有高能量需求和代谢灵活性的器官,其代谢依赖于脂肪酸的氧化作为产生腺苷三磷酸(ATP)的主要来源。

丙酮酸是心肌和其他组织中广泛存在的一种天然代谢燃料和抗氧化物质,能够增强心肌收缩性能和心肌能量状态。不过,它必须通过线粒体丙酮酸载体(MPC)进行转运,后者是MPC1和MPC2蛋白组成的异源低聚物,也是心力衰竭中解偶联糖酵解和葡萄糖氧化的代谢中枢。

在由圣路易斯大学Kyle S. McCommis教授领导的研究中,研究人首先对比了患有与不患有心脏衰竭的人和小鼠心脏中的MPC蛋白表达,发现在衰竭的人和小鼠心脏中MPC表达降低,并且小鼠中MPC的基因缺失导致心脏重塑和功能障碍。

心衰时MPCs下调,心肌MPC2缺失导致TCA循环功能障碍

随后,研究人员敲除了小鼠心脏的Mpc2基因,此时丙酮酸刺激的氧消耗率(OCR)显着降低,并且心肌MPC的丢失导致线粒体丙酮酸代谢缺陷,三羧酸(TCA)循环流量的改变以及氧化还原状态的潜在失调。尽管超声图显示小鼠在6周龄的时候心脏正常,但之后逐渐出现心脏重塑和功能障碍。

为了验证饮食是否能够改善Mpc2基因缺失小鼠的心脏重塑和功能障碍,研究人员在小鼠6周龄至17周龄期间分别以低脂饮食(LF)、生酮饮食(KD)、低碳水化合物饮食对它们进行饲养。

结果显示,生酮饮食组在10周龄和16周龄的超声心动图显示出几乎正常的心脏大小和功能,而低脂饮食组则显示出严重心脏功能不全。在17周龄时,生酮饮食组小鼠全都存活下来了,但是低脂饮食组存活率仅为65%。不过,研究人员发现,这样的效果似乎并不是由酮体代谢带来的,而是刺激了脂肪酸氧化(FAO)所产生的效果。

更加令人惊喜的是,研究人员发现生酮饮食显示出逆转心力衰竭的潜力,即使是16周大、已经显示出心脏扩张和收缩功能变差的Mpc2基因缺失小鼠,以生酮饮食的方式喂养3周后病情仍然得到有效改善。

KD能逆转CS-Mpc2 a心力衰竭逆转实验的时间轴

在另一项研究中,爱荷华大学卡佛医学院的研究人员敲除了小鼠的MPC1基因,并观察到小鼠出现了心肌肥厚、心力衰竭和过早死亡的情况,在进一步实验中,研究人员发现,生酮饮食或高脂饮食均能逆转非应激性的MPC1基因缺陷小鼠的心脏结构,重塑其功能。

选择性底物喂养可逆转小鼠心脏功能不全

当然,生酮饮食并不是万能的,研究人员发现,只有在发生主动脉狭窄之前进行3周生酮饮食才能够起到保护作用。

总之,这两项研究揭示了线粒体丙酮酸在调节心脏基础代谢和功能方面的核心作用,饮食干预或许是提高脂肪酸代谢以逆转心脏功能不全和重塑的潜在方案。

原始出处:

[1]Kyle S McCommis, Attila Kovacs, Carla J Weinheimer, et al.Nutritional modulation of heart failure in mitochondrial pyruvate carrier-deficient mice.Nat Metab. 2020 Oct 26. doi: 10.1038/s42255-020-00296-1.

[2]Yuan Zhang, Paul V Taufalele, Jesse D Cochran, et al.Mitochondrial pyruvate carriers are required for myocardial stress adaptation.Nat Metab. 2020 Oct 26. doi: 10.1038/s42255-020-00288-1. 

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    2021-04-08 liye789132251
  2. [GetPortalCommentsPageByObjectIdResponse(id=1884777, encodeId=deab1884e77be, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Thu Apr 08 04:00:16 CST 2021, time=2021-04-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1896771, encodeId=057c1896e7192, content=<a href='/topic/show?id=4a391158248' target=_blank style='color:#2F92EE;'>#MET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11582, encryptionId=4a391158248, topicName=MET)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=18fc139, createdName=一闲, createdTime=Sun Dec 13 00:00:16 CST 2020, time=2020-12-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=897236, encodeId=f88e89e23640, content=直接静脉给予酮体呢?, beContent=null, objectType=article, channel=null, level=null, likeNumber=67, replyNumber=1, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/oLAjfB7s1ib06iaV3D9Tg5K2dZHgwLr8w3alNsJUwW9Wcgn9BHDLZ2FO9rnayy0ooRWhsAibFokXweeicibQVSrwia1x5UlYibpwkCM/0, createdBy=3bf1106371, createdName=longlaneblake, createdTime=Fri Nov 06 00:26:45 CST 2020, time=2020-11-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1888235, encodeId=8b3018882353c, content=<a href='/topic/show?id=d56611584ec' target=_blank style='color:#2F92EE;'>#Meta#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11584, encryptionId=d56611584ec, topicName=Meta)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d8f4110, createdName=guojianrong, createdTime=Thu Aug 26 06:00:16 CST 2021, time=2021-08-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=897161, encodeId=1bdf89e16144, content=生酮饮食或可预防甚至逆转心力衰竭, beContent=null, objectType=article, channel=null, level=null, likeNumber=78, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=51725431630, createdName=ms4000001069884556, createdTime=Thu Nov 05 16:54:32 CST 2020, time=2020-11-05, status=1, ipAttribution=)]
    2020-12-13 一闲
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    2020-11-06 longlaneblake

    直接静脉给予酮体呢?

    1

    展开1条回复
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    2021-08-26 guojianrong
  5. [GetPortalCommentsPageByObjectIdResponse(id=1884777, encodeId=deab1884e77be, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Thu Apr 08 04:00:16 CST 2021, time=2021-04-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1896771, encodeId=057c1896e7192, content=<a href='/topic/show?id=4a391158248' target=_blank style='color:#2F92EE;'>#MET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11582, encryptionId=4a391158248, topicName=MET)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=18fc139, createdName=一闲, createdTime=Sun Dec 13 00:00:16 CST 2020, time=2020-12-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=897236, encodeId=f88e89e23640, content=直接静脉给予酮体呢?, beContent=null, objectType=article, channel=null, level=null, likeNumber=67, replyNumber=1, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/oLAjfB7s1ib06iaV3D9Tg5K2dZHgwLr8w3alNsJUwW9Wcgn9BHDLZ2FO9rnayy0ooRWhsAibFokXweeicibQVSrwia1x5UlYibpwkCM/0, createdBy=3bf1106371, createdName=longlaneblake, createdTime=Fri Nov 06 00:26:45 CST 2020, time=2020-11-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1888235, encodeId=8b3018882353c, content=<a href='/topic/show?id=d56611584ec' target=_blank style='color:#2F92EE;'>#Meta#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11584, encryptionId=d56611584ec, topicName=Meta)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d8f4110, createdName=guojianrong, createdTime=Thu Aug 26 06:00:16 CST 2021, time=2021-08-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=897161, encodeId=1bdf89e16144, content=生酮饮食或可预防甚至逆转心力衰竭, beContent=null, objectType=article, channel=null, level=null, likeNumber=78, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=51725431630, createdName=ms4000001069884556, createdTime=Thu Nov 05 16:54:32 CST 2020, time=2020-11-05, status=1, ipAttribution=)]
    2020-11-05 ms4000001069884556

    生酮饮食或可预防甚至逆转心力衰竭

    0

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