Burke L K, Heisler L K
Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen, UK.
Department of Pharmacology, University of Cambridge, Cambridge, UK.
J Neuroendocrinol. 2015 Jun;27(6):389-98. doi: 10.1111/jne.12287.
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 15 years. 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-HT2 C R as the principal 5-HTR mediating this homeostatic process. Capitalising on this neurophysiological machinery, 5-HT2 C R 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-HT2 C R modulation of the brain melanocortin circuit via activation of pro-opiomelanocortin neurones signalling at melanocortin4 receptors. Thus, 5-HT2 C R agonists offer a means to improve obesity and type 2 diabetes, which are conditions that now represent global challenges to human health.
中枢5-羟色胺（5-HT；血清素）系统是大脑控制能量平衡的一个基本组成部分。在过去15年里，针对5-HT途径的药物一直处于肥胖治疗的前沿。靶向5-HT受体（5-HTR）的药物，与5-HTR操纵的遗传模型相结合，揭示了特定5-HTR在能量平衡中的作用，并表明5-HT2 C R是介导这一稳态过程的主要5-HTR。利用这种神经生理机制，5-HT2 C R激动剂可改善患者群体的肥胖和血糖控制。已使用模型系统探究了其潜在的治疗机制，似乎主要是通过5-HT2 C R对脑黑皮质素回路的调节来实现的，该调节是通过激活在黑皮质素4受体发出信号的促阿片黑素皮质素神经元来实现的。因此，5-HT2 C R激动剂提供了一种改善肥胖和2型糖尿病的方法，而肥胖和2型糖尿病目前对人类健康构成全球性挑战。
