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阿尔兹海默病新突破！人体内的脂肪竟成AD患者新福音

2021-09-28 李乐一 MedSci原创

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阿尔兹海默症（AD）是一种以认知能力丧失为特征的神经退行性疾病。它主要发病于老年人：85岁以上人口中约占30%。女性也比男性更容易患上痴呆症。 目前AD已成为仅次于心血管疾病、脑卒中和癌症的

阿尔兹海默症（AD）是一种以认知能力丧失为特征的神经退行性疾病。它主要发病于老年人：85岁以上人口中约占30%。女性也比男性更容易患上痴呆症。 目前AD已成为仅次于心血管疾病、脑卒中和癌症的第四大死亡疾病。
 
由于AD的发病机制十分复杂，发病过程涉及环节较多，现如今并没有什么治疗手段可以阻止或逆转AD的“横行霸道”，仅有少部分疗法可能会暂缓其症状。
通过以往的数据，我们可以发现，AD最重要的致病因素是高龄。
 
年龄在机体的热量产生和热量损失之间起着重要的平衡作用。随着年龄的增长，我们的体温调节机制可能会变得效率低下。并且，科学家们发现，老年患者在由于代谢失调而引发AD的过程中，往往伴随着体温调节缺陷的发生。
那么AD与体温调节缺陷具有何种“剪不断、理还乱”的关系呢？
 
近期，一项发表在《Ageing Research Reviews》开放期刊上的评论，对AD与体温调节展开讨论，利用目前的研究进展总结了体温调节缓解AD的潜在药物疗法。研究员发现促进棕色脂肪组织产热，可改善体温来减缓AD的症状，从而成为AD的潜在治疗方法！
图片
https://doi.org/10.1016/j.arr.2021.101462
 
作者认为，衰老是AD发生的重要因素，同时身体的衰老会减慢代谢，引发肥胖等代谢性疾病；另一方面，这些代谢性疾病也会进一步加重AD患者的病情。
 
在这样的“恶性循环”中，体温调节缺陷身为代谢不良的关键组成部分，也不甘示弱，不仅干扰了大脑的能量利用，还加重了前文介绍的AD病理学特征，在整个病情中扮演了“推波助澜”的角色。
衰老、体温调节缺陷、代谢紊乱和阿尔茨海默症之间的病理循环
 
那么，如何能让体温调节走向“正途”呢？
 
这里就需要隆重介绍一下人体一个重要组成部分——棕色脂肪组织（BAT），一个低调却又至关重要的产热器官。BAT主要存在于人的颈部、锁骨、肾脏和脊髓等区域。
                                                                     PET-CT扫描显示，左边的受试者颈部和脊柱一带的棕色脂肪组织比例较大，洛克菲勒大学
说它“低调”，是因为它往往只有几克重；说它“重要”，则是因为当它被激活时，会利用血液中的糖和脂肪在体内产生热量。这热量不仅是改善我们体温的“灵丹妙药”，还能改善血糖血脂水平，令人体紊乱的代谢得以恢复正常！
 
因此，促进BAT产热，不仅可以治好AD患者的代谢问题，还可以通过改善体温来减缓AD的病理学三大表征，双管齐下，从而成为AD的潜在治疗方法！
图片
                                                        刺激BAT产热可以改善AD病理
 
那么如何刺激BAT产热从而改善AD患者的病情呢？
 
在本文中，作者总结归纳了6种可以通过调节BAT功能从而改善AD的激素，包括胰岛素（保持大脑葡萄糖摄取）、脂联素（促进神经发生）、瘦素（利于记忆保留）、成纤维细胞生长因子21 （改善新陈代谢）、甲状腺激素（改善新陈代谢）和褪黑激素（利于记忆保留）。
 
基于BAT产热调节AD这一思路，作者认为可以开发新的治疗策略。该策略分为两种：非药物疗法和药物疗法。
 
非药物疗法包括：通过维持环境温度来维持体温，以及人们“喜闻乐见”的锻炼运动法。
 
在运动过程中，人体会产生一种叫做鸢尾素的分子，它可以驱动人体的白色脂肪组织向棕色脂肪组织的特征转变，从而促进机体产热，改善体温，达到治疗AD的目的。
 
药物疗法即用药物刺激BAT产热：β3AR激动剂是直接刺激产热的常用方法，然而在临床环境中是否可以采用β3AR激动剂治疗中老年人仍然存在争议。
 
总之，体温是老年人新陈代谢的最基本标志之一，人体温度大约与AD发病率成反比。由于BAT在体温调节中的核心作用，增加BAT产热可以恢复体温调节，改善代谢参数（例如：胰岛素抵抗），并缓解AD的病理学特征。由此看来，“生命在于运动”这句话是极正确的呢~
参考文献
[1] Evidence for brain glucose dysregulation in Alzheimer's disease. Alzheimers Dement. 2018 Mar;14(3):318-329. DOI: 10.1016/j.jalz.2017.09.011.
[2] Irisin exerts dual effects on browning and adipogenesis of human white adipocytes. Am J Physiol Endocrinol Metab. 2016 Aug 1;311(2): E530-41. DOI: 10.1152/ajpendo.00094.
[3] Brain energy rescue: an emerging therapeutic concept for neurodegenerative disorders of ageing. Nat Rev Drug Discov. 2020 Sep;19(9):609-633. DOI: 10.1038/s41573-020-0072-x. 

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    2022-08-29 zxxiang

    #新突破#

    0

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    2021-09-30 habb

    #阿尔兹海默#

    0

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    2021-09-28 ms1000002136354097

    怎样增加棕色脂肪呢

    0

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    2021-09-28 ZYY7209

    不错

    0

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    2021-09-28 大叔默默路过

    不错的进展

    0