西亚试剂：Selective Receptor Agonists for the Treatment of Obesity

发布时间：2026-02-07

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.

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