肥胖病现在是世界性流行病，我国不论肥胖成人或小孩都在增多。但至今没有一个满意的药物，铺天盖地的减肥保健品广告并不可靠，正式批准的两个药物之一――西布曲明最近也出了点问题。
肥胖的根本问题是进食热卡过剩及消耗代谢不足，这两者都是由中枢神经控制的。自从发现瘦素以后，本以为能解决肥胖问题，实际上却无效。以后相继又发现了许多有关物质，如黑皮素、神经肽Y、内源大麻酚样通道等，但疗效均有限，说明存在多种代偿通道。
2010年2月著名的《细胞代谢》杂志发表管小明等研究者的文章。他们首次找到能与铃蟾素受体亚型3（BRS-3）结合的物质，并深入研究。BRS-3在自然界或人体内与什么配体相结合，至今未明。仅仅在1997年有人用基因方法知道鼠的BRS-3与代谢有关。此次管小明等发现，能与BRS-3强有力结合的有高度选择性的非肽类配体，而且能够口服，他们称之为Bag-I，这是一种促效剂。他们也发现了拮抗剂配体，称为Bantag-I。
管小明等对大鼠脑室内滴注Bantag-I12天，可使摄食增加12%，体重自50.2克增至69.4克，增加的主要是脂肪组织。给小鼠口服Bag-I30mg/kg及100mg/kg，小剂量者未见体重下降，高剂量者对一般小鼠减少体重5%，而对因过食致肥者减少体重11%。对肥胖鼠低剂量者也减少6%，而且高剂量组可见进食减少23%。小鼠在禁食时一般会自行减少能量消耗约30%，但用Bag-I后仍可增加能量消耗，约维持10小时。Bag-I对杂饲鼠增加空腹能量消耗约20%。
应用放射性Bag，用放射自显影法可见下丘脑、前脑、尾脑及杏仁核和丘脑都有中到高度BRS-3结合，说明此受体主要分布在这些部位，与摄食及代谢有关。另外还发现多巴胺能及血清素能神经元密度也有少量结合。口服Bag-I后在1、6及20小时脑内BRS-3的占有率各为80%、28%及&10%，说明其半寿期短。
另外他们用分别敲除有关摄食等各通道基因的小鼠做实验，仍能使进食减少，说明这些通道与BRS-3可能是互补的，并不重复。
该杂志的编者对此文很重视，请剑桥大学Coll教授写了评论。Coll认为此工作很好，很有希望。但如果进入临床，还有些工作要做，例如副作用问题。尽管该文作者对大鼠作复杂迷宫试验，证明对行为学无影响。但人究竟与鼠不同，将来临床研究证明副作用小，才能推广应用。
生物谷推荐原文出处：
Cell Metabolism DOI: 10.1016/j.cmet.2009.12.008
Regulation of Energy Homeostasis by Bombesin Receptor Subtype-3: Selective Receptor Agonists for the Treatment of Obesity
Xiao-Ming Guan, Howard Chen, Peter H. Dobbelaar, Yan Dong, Tung M. Fong, Karen Gagen, Judith Gorski, Shuwen He, Andrew D. Howard, Tianying Jian, Michael Jiang, Yanqing Kan, Theresa M. Kelly, Jennifer Kosinski, Linus S. Lin, Jian Liu, Donald J. Marsh, Joseph M. Metzger, Randy Miller, Ravi P. Nargund, Oksana Palyha, Lauren Shearman, Zhu Shen, Ralph Stearns, Alison M. Strack, Sloan Stribling, Yui Sing Tang, Sheng-Ping Wang, Amanda White, Hong Yu, Marc L. Reitman
Bombesin receptor subtype 3 (BRS-3) is a G protein coupled receptor whose natural ligand is unknown. We developed potent, selective agonist (Bag-1, Bag-2) and antagonist (Bantag-1) ligands to explore BRS-3 function. BRS-3-binding sites were identified in the hypothalamus, caudal brainstem, and several midbrain nuclei that harbor monoaminergic cell bodies. Antagonist administration increased food intake and body weight, whereas agonists increased metabolic rate and reduced food intake and body weight. Prolonged high levels of receptor occupancy increased weight loss, suggesting a lack of tachyphylaxis. BRS-3 agonist effectiveness was absent in Brs3?/Y (BRS-3 null) mice but was maintained in Npy/Agrp/, Mc4r, Cnr1, and Leprdb/db mice. In addition, Brs3?/Y mice lost weight upon treatment with either a MC4R agonist or a CB1R inverse agonist. These results demonstrate that BRS-3 has a role in energy homeostasis that complements several well-known pathways and that BRS-3 agonists represent a potential approach to the treatment of obesity.
