Ellacott Kate L J, Cone Roger D
Vollum Institute, Oregon Health and Science University, Portland, Oregon 97239-3098, USA.
Recent Prog Horm Res. 2004;59:395-408. doi: 10.1210/rp.59.1.395.
The importance of the central melanocortin system in the regulation of energy balance is highlighted by studies in transgenic animals and humans with defects in this system. Mice that are engineered to be deficient for the melanocortin-4 receptor (MC4R) or pro-opiomelanocortin (POMC) and those that overexpress agouti or agouti-related protein (AgRP) all have a characteristic obese phenotype typified by hyperphagia, increased linear growth, and metabolic defects. Similar attributes are seen in humans with haploinsufficiency of the MC4R. The central melanocortin system modulates energy homeostasis through the actions of the agonist, alpha-melanocyte-stimulating hormone (alpha-MSH), a POMC cleavage product, and the endogenous antagonist AgRP on the MC3R and MC4R. POMC is expressed at only two locations in the brain: the arcuate nucleus of the hypothalamus (ARC) and the nucleus of the tractus solitarius (NTS) of the brainstem. This chapter will discuss these two populations of POMC neurons and their contribution to energy homeostasis. We will examine the involvement of the central melanocortin system in the incorporation of information from the adipostatic hormone leptin and acute hunger and satiety factors such as peptide YY (PYY(3-36)) and ghrelin via a neuronal network involving POMC/cocaine and amphetamine-related transcript (CART) and neuropeptide Y (NPY)/AgRP neurons. We will discuss evidence for the existence of a similar network of neurons in the NTS and propose a model by which this information from the ARC and NTS centers may be integrated directly or via adipostatic centers such as the paraventricular nucleus of the hypothalamus (PVH).
对转基因动物和该系统存在缺陷的人类的研究突出了中枢黑皮质素系统在能量平衡调节中的重要性。经过基因工程改造而缺乏黑皮质素-4受体（MC4R）或阿黑皮素原（POMC）的小鼠，以及那些过表达刺鼠信号蛋白或刺鼠相关蛋白（AgRP）的小鼠，都具有以食欲亢进、线性生长增加和代谢缺陷为典型特征的肥胖表型。在MC4R单倍剂量不足的人类中也观察到类似特征。中枢黑皮质素系统通过激动剂α-黑素细胞刺激素（α-MSH，一种POMC裂解产物）和内源性拮抗剂AgRP对MC3R和MC4R的作用来调节能量稳态。POMC仅在大脑中的两个位置表达：下丘脑弓状核（ARC）和脑干孤束核（NTS）。本章将讨论这两类POMC神经元及其对能量稳态的贡献。我们将研究中枢黑皮质素系统如何通过一个涉及POMC/可卡因和苯丙胺调节转录肽（CART）以及神经肽Y（NPY）/AgRP神经元的神经网络，整合来自脂肪稳态激素瘦素以及急性饥饿和饱腹感因子（如肽YY（PYY(3-36)）和胃饥饿素）的信息。我们将讨论NTS中存在类似神经元网络的证据，并提出一个模型，通过该模型，来自ARC和NTS中心的这些信息可以直接整合，或通过诸如下丘脑室旁核（PVH）等脂肪稳态中心进行整合。
