The neuroendocrine circuitry controlled by POMC, MSH, and AGRP.
The neuroendocrine circuitry controlled by POMC, MSH, and AGRP.
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DOI：
10.1007/978-3-642-24716-3_3
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发表时间：
2012-01-01
影响因子：
--
通讯作者：
Krude, Heiko
中科院分区：
文献类型：
--
作者：
Biebermann, Heike;Kuhnen, Peter;Krude, Heiko
肥胖是全球最具挑战性的健康问题之一。在过去的几十年里，我们的知识有关的体重调节机制已经大大增加，导致瘦素-黑皮质素途径的鉴定。能量储存的填充水平向大脑发出信号，信息由下丘脑核团整合，导致对食物摄入和能量消耗的精心协调的反应，以确保恒定的体重。该系统中的关键参与者之一是阿黑皮素原（POMC），它是多种神经肽的前体。POMC衍生的α-和β-MSH通过激活在弓状核（MC 3R）和室旁核（MC 4 R）中表达的黑皮质素受体在能量稳态中起重要作用。这两种G蛋白偶联受体的激活被刺豚鼠相关肽（AgRP）拮抗。在患有普通肥胖症的患者以及表现出严重早发性肥胖症、肾上腺功能不全、红头发和苍白皮肤表型的患者中鉴定了该系统中天然发生的突变。详细了解POMC-AgRP-MC 3R-MC 4 R复杂系统及其与其他下丘脑和外周信号的相互作用是对抗肥胖流行病的先决条件。
Obesity is one of the most challenging health problems worldwide. Over the past few decades, our knowledge concerning mechanisms of weight regulation has increased tremendously leading to the identification of the leptin-melanocortin pathway. The filling level of energy stores is signaled to the brain, and the information is integrated by hypothalamic nuclei, resulting in a well-orchestrated response to food intake and energy expenditure to ensure constant body weight. One of the key players in this system is proopiomelanocortin (POMC), a precursor of a variety of neuropeptides. POMC-derived alpha- and beta-MSH play an important role in energy homeostasis by activating melanocortin receptors expressed in the arcuate nucleus (MC3R) and in the nucleus paraventricularis (MC4R). Activation of these two G protein-coupled receptors is antagonized by agouti-related peptide (AgRP). Naturally occurring mutations in this system were identified in patients suffering from common obesity as well as in patients demonstrating a phenotype of severe early-onset obesity, adrenal insufficiency, red hair, and pale skin. Detailed understanding of the complex system of POMC-AgRP-MC3R-MC4R and their interaction with other hypothalamic as well as peripheral signals is a prerequisite to combat the obesity epidemic.