Mice lacking bombesin receptor subtype-3 develop metabolic defects and obesity

✍ Scribed by Ohki-Hamazaki, Hiroko; Wada, Keiji; Watase, Kei; Yamamoto, Kazutoshi; Ogura, Hiroo; Yamano, Mariko; Yamada, Kazuyuki; Maeno, Hiroshi; Imaki, Junko; Kikuyama, Sakae; Wada, Etsuko

• Book ID: 109786576
• Publisher: Nature Publishing Group
• Year: 1997
• Tongue: English
• Weight: 386 KB
• Volume: 390
• Category: Article
• ISSN: 0028-0836
• DOI: 10.1038/36568

✦ Synopsis

Mammalian bombesin-like peptides are widely distributed in the central nervous system as well as in the gastrointestinal tract, where they modulate smooth-muscle contraction, exocrine and endocrine processes, metabolism and behaviour. They bind to G-protein-coupled receptors on the cell surface to elicit their effects. Bombesin-like peptide receptors cloned so far include, gastrin-releasing peptide receptor (GRP-R), neuromedin B receptor (NMB-R), and bombesin receptor subtype-3 (BRS-3). However, despite the molecular characterization of BRS-3, determination of its function has been difficult as a result of its low affinity for bombesin and its lack of an identified natural ligand. We have generated BRS-3-deficient mice in an attempt to determine the in vivo function of the receptor. Mice lacking functional BRS-3 developed a mild obesity, associated with hypertension and impairment of glucose metabolism. They also exhibited reduced metabolic rate, increased feeding efficiency and subsequent hyperphagia. Our data suggest that BRS-3 is required for the regulation of endocrine processes and metabolism responsible for energy balance and adiposity. BRS-3-deficient mice provide a useful new model for the investigation of human obesity and associated diseases.