Physiological roles for butyrylcholinesterase: A BChE-ghrelin axis.
Physiological roles for butyrylcholinesterase: A BChE-ghrelin axis.
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DOI：
10.1016/j.cbi.2016.02.013
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发表时间：
2016-11-25
影响因子：
5.1
通讯作者：
Gao Y
中科院分区：
文献类型：
--
作者：
Brimijoin S;Chen VP;Pang YP;Geng L;Gao Y
丁酰胆碱酯酶（BChE）一直被认为是一种“孤儿酶”，除了代谢饮食或药物中的外源性生物活性酯外，没有特异的生理作用。具有消除所有BChE活性的基因突变的人类似乎完全正常，BChE敲除小鼠被描述为“缺乏表型”，除了在高脂肪饮食中体重增加更快。然而，我们最近在小鼠中进行的BChE病毒基因转移研究表明，BChE水解所谓的“饥饿激素”ghrelin，其速率强烈影响这种肽激素的循环水平。这种作用对体重增加和脂肪代谢有重要影响。令人惊讶的是，它也影响了情绪行为，如攻击性。BChE的过度表达导致血液中ghrelin水平降低，并减少小鼠的攻击性和社会压力。在某些情况下，这些综合效应有助于延长群养动物的寿命。这些发现可能适用于人类，因为多名研究人员最近的临床研究表明，在患有严重心血管疾病的患者中，长寿与血浆BChE活性水平的增加相关。
Butyrylcholinesterase (BChE) has long been regarded as an “orphan enzyme” with no specific physiological role other than to metabolize exogenous bioactive esters in the diet or in medicines. Human beings with genetic mutations that eliminate all BChE activity appear completely normal, and BChE-knockout mice have been described as “lacking a phenotype” except for faster weight gain on high-fat diets. However, our recent studies with viral gene transfer of BChE in mice reveal that BChE hydrolyses the so-called “hunger hormone,” ghrelin, at a rate which strongly affects the circulating levels of this peptide hormone. This action has important consequences for weight gain and fat metabolism. Surprisingly, it also impacts emotional behaviors such as aggression. Overexpression of BChE leads to low ghrelin levels in the blood stream and reduces aggression and social stress in mice. Under certain circumstances these combined effects contribute to increased life-span in group-housed animals. These findings may generalize to humans, as recent clinical studies by multiple investigators indicate that, among patients with severe cardiovascular disease, longevity correlates with increasing levels of plasma BChE activity.