H Ohki-Hamazaki, K Watase, K Yamamoto, H Ogura, M Yamano, K Yamada, H Maeno, J Imaki, S Kikuyama, E Wada, K Wada
Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan. hamazaki@prit.go.jp
Nature 1997 Nov 13Mammalian 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.
H Ohki-Hamazaki, K Watase, K Yamamoto, H Ogura, M Yamano, K Yamada, H Maeno, J Imaki, S Kikuyama, E Wada, K Wada. Mice lacking bombesin receptor subtype-3 develop metabolic defects and obesity. Nature. 1997 Nov 13;390(6656):165-9
PMID: 9367152
View Full Text