Zac-Varghese Sagen, Tan Tricia, Bloom Stephen Robert
Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Imperial College London, London, United Kingdom.
Discov Med. 2010 Dec;10(55):543-52.
No truly effective drugs exist to treat obesity, which is reaching pandemic proportions. The search for new treatments has led to an interest into the homeostatic system of central appetite regulation. Key components of this system include the hypothalamus and brainstem, the gut, and adipose tissue. It is now recognized that food intake leads to the release of various gut hormones. There are several anorectic (appetite suppressing) gut hormones released, including cholecystokinin, glucagon like peptide-1, oxyntomodulin, peptide tyrosine tyrosine, and pancreatic polypeptide. To date, only one example is known of an orexigenic (appetite stimulating) hormone, ghrelin. These hormones circulate in the blood and signal via vagal nerve afferents to communicate with the hypothalamus and brainstem. This information is integrated and processed in key hypothalamic nuclei. The arcuate nucleus appears to be a central controller of the appetite circuit, integrating both peripheral and central signals. This information is translated into downstream signals affecting body metabolism and food intake. Increased understanding and successful manipulation of this system should enable the design of a successful and much needed anti-obesity treatment.
目前还没有真正有效的药物来治疗肥胖症,而肥胖症正呈流行趋势。对新治疗方法的探索引发了人们对中枢食欲调节稳态系统的兴趣。该系统的关键组成部分包括下丘脑和脑干、肠道以及脂肪组织。现在人们认识到食物摄入会导致各种肠道激素的释放。释放的几种抑制食欲的肠道激素包括胆囊收缩素、胰高血糖素样肽 -1、胃泌酸调节素、肽酪酪肽和胰多肽。迄今为止,已知的一种刺激食欲的激素只有胃饥饿素。这些激素在血液中循环,并通过迷走神经传入信号与下丘脑和脑干进行通信。这些信息在关键的下丘脑核中进行整合和处理。弓状核似乎是食欲回路的中央控制器,整合外周和中枢信号。这些信息被转化为影响身体代谢和食物摄入的下游信号。对该系统的深入了解和成功操控应该能够设计出一种成功且急需的抗肥胖治疗方法。