5-Hydroxytryptamine Medications for the Treatment of Obesity
5-Hydroxytryptamine Medications for the Treatment of Obesity
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DOI：
10.1111/jne.12287
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发表时间：
2015-06-01
影响因子：
3.2
通讯作者：
Heisler, L. K.
中科院分区：
文献类型：
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作者：
Burke, L. K.;Heisler, L. K.
中枢5-羟色胺（5-HT;血清素）系统代表了大脑控制能量稳态的基本组成部分。在过去的15年里，针对5-HT通路的药物一直处于肥胖治疗的最前沿。靶向5-HT受体（5-HTR）的药理学试剂与5-HTR操纵的遗传模型结合，已经揭示了特定5-HTR在能量平衡中的作用，并揭示了5-HT 2CR作为介导该稳态过程的主要5-HTR。利用这种神经生理机制，5-HT 2CR激动剂改善患者人群的肥胖和血脂控制。已经使用模型系统探索了潜在的治疗机制，并且似乎主要通过激活黑皮质素4受体处的前阿黑皮素神经元信号传导，通过脑黑皮质素回路的5-HT 2CR调节来实现。因此，5-HT 2CR激动剂提供了一种改善肥胖和2型糖尿病的方法，这些疾病现在代表着对人类健康的全球挑战。
The central 5-hydroxytryptamine (5-HT; serotonin) system represents a fundamental component of the brain's control of energy homeostasis. Medications targeting the 5-HT pathway have been at the forefront of obesity treatment for the past 15years. Pharmacological agents targeting 5-HT receptors (5-HTR), in combination with genetic models of 5-HTR manipulation, have uncovered a role for specific 5-HTRs in energy balance and reveal the 5-HT2CR as the principal 5-HTR mediating this homeostatic process. Capitalising on this neurophysiological machinery, 5-HT2CR agonists improve obesity and glycaemic control in patient populations. The underlying therapeutic mechanism has been probed using model systems and appears to be achieved primarily through 5-HT2CR modulation of the brain melanocortin circuit via activation of pro-opiomelanocortin neurones signalling at melanocortin4 receptors. Thus, 5-HT2CR agonists offer a means to improve obesity and type 2 diabetes, which are conditions that now represent global challenges to human health.