Review Of NPY And NPY Receptor For Obesity

Daxesh P. Patel, N. Patel
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引用次数: 4

Abstract

The prevalence of obesity continues to increase throughout the world and the burden of obesity and related co morbidities is large. However existing drug therapies for obesity are limited and agents with high efficacy, safety and tolerability are expected to meet patient needs and lead to more substantial commercial success. Contemporary consideration has focused on physiology of neuropeptides Y (NPY) and its role in the regulation of energy homeostasis. NPY stimulates food intake, inhibits energy expenditure, and increases body weight and increases anabolic hormone level by activating the NPY Y1 and Y5 receptors in the hypothalamus. Based on these findings, several NPY Y1 and Y5 receptor antagonists have been developed in last two decade as potential anti-obesity agents and transgenic mice model lacking NPY, the NPY Y1 receptor or the NPY Y5 receptor have been generated. The data obtained to date with these newly developed tools suggests that NPY receptor antagonists, particularly NPY Y1 and Y5 receptor antagonist, have potentiality to bless the obesity patients worldwide. However, the redundancy of the neurochemical systems regulating energy homeostasis may limit the effect of ablating a single pathway. In addition, patients in whom the starvation response is activated, such as formerly obese patients who have lost weight or patients with complete or partial leptin deficiency, may be the best candidates for treatment with a NPY receptor antagonist. New leads are under research by major pharmaceutical companies to limit the side effects and explore the area to meet clinical requirement.
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肥胖症NPY及其受体研究进展
肥胖的患病率在世界范围内持续增加,肥胖和相关并发症的负担很大。然而,现有的肥胖药物治疗是有限的,高效、安全和耐受性强的药物有望满足患者的需求,并取得更大的商业成功。目前的研究主要集中在神经肽Y (NPY)的生理学及其在能量稳态调节中的作用。NPY通过激活下丘脑的NPY Y1和Y5受体,刺激食物摄入,抑制能量消耗,增加体重,提高合成代谢激素水平。基于这些发现,在过去的二十年中,一些NPY Y1和Y5受体拮抗剂作为潜在的抗肥胖药物被开发出来,并产生了缺乏NPY、NPY Y1受体或NPY Y5受体的转基因小鼠模型。迄今为止,这些新开发的工具获得的数据表明,NPY受体拮抗剂,特别是NPY Y1和Y5受体拮抗剂,有可能造福全世界的肥胖患者。然而,调节能量稳态的神经化学系统的冗余可能会限制单个通路的消融效果。此外,饥饿反应被激活的患者,如体重减轻的前肥胖患者或完全或部分瘦素缺乏的患者,可能是使用NPY受体拮抗剂治疗的最佳人选。大型制药公司正在研究新的先导药物,以限制副作用并探索满足临床需求的领域。
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