Juhász Attila, Katona Evelin, Csongrádi Eva, Paragh György
Sopron MJV Erzsébet Kórház, a DE OEC Oktató Kórháza Belgyógyászat Sopron Gyori.
Orv Hetil. 2007 Sep 30;148(39):1827-36. doi: 10.1556/OH.2007.28085.
Body mass--strictly speaking: the adipose tissue mass--is regulated in a feed-back system by the hypothalamus and brainstem, where adiposity signals (leptin, insulin, amylin) and intestinal peptides (ghrelin, PYY, PP, GLP-1, OXM, CCK) and the vagal nerve provide afferent information to the central controller on the size of white adipose tissue and the actual nutritional state, respectively. Two distinct groups of neurons in the arcuate nucleus accept and process the afferent information provided by leptin produced by white adipocytes in proportion to their mass. Leptin binding to the leptin-receptors on the surface of these neurons initiates intracellular signal transduction and activation of target genes, resulting in the synthesis and release of neuropeptides (POMC, CART) with anorectic effects. Secondary centers in the brain are also activated, and finally integrated effector mechanisms are generated in order to regulate the balance between energy intake and expenditure. The regulation of body weight is carried out by the central nervous system in a complex and redundant way, characterized by interconnections and overlaps with other neuroendocrine functions, such as growth, thyroid and adrenal function, memory, addictive and reward mechanisms. Targeting one or another component of this complicated system with drugs might result in interference with other systems and functions, so the occurrence of adverse events is probable. The worldwide epidemic of obesity--resulting mostly from the abundance of energy-dense foods and sedentary lifestyle coupled with a regulatory system unable to cope with this environment--has resulted in a continuous increase of research activities in both academic and industrial centers to develop new drugs and treatment strategies beyond lifestyle changes (diet, physical activity and behavioral therapy) to fight obesity more effectively.
体重——严格来说是脂肪组织量——由下丘脑和脑干通过反馈系统进行调节。在该系统中，肥胖信号（瘦素、胰岛素、胰淀素）、肠道肽（胃饥饿素、肽YY、胰多肽、胰高血糖素样肽-1、氧代甲肾上腺素、胆囊收缩素）以及迷走神经分别向中央控制器提供关于白色脂肪组织大小和实际营养状态的传入信息。弓状核中的两组不同神经元接收并处理白色脂肪细胞按其质量比例产生的瘦素所提供的传入信息。瘦素与这些神经元表面的瘦素受体结合，启动细胞内信号转导并激活靶基因，导致具有厌食作用的神经肽（促黑素细胞皮质激素、可卡因-安非他明调节转录肽）的合成与释放。大脑中的二级中枢也被激活，最终产生综合效应机制以调节能量摄入与消耗之间的平衡。体重调节由中枢神经系统以复杂且冗余的方式进行，其特点是与其他神经内分泌功能（如生长、甲状腺和肾上腺功能、记忆、成瘾和奖赏机制）相互关联且相互重叠。用药物靶向这个复杂系统的一个或另一个组成部分可能会干扰其他系统和功能，所以很可能会出现不良事件。全球肥胖流行——主要是由于能量密集型食物丰富、久坐不动的生活方式以及调节系统无法应对这种环境——导致学术和工业中心的研究活动持续增加，以开发除生活方式改变（饮食、体育活动和行为疗法）之外的新药和治疗策略，从而更有效地对抗肥胖。
