Mice lacking bombesin receptor subtype-3 develop metabolic defects and obesity.
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.
Ohki-Hamazaki
H
H
Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan. hamazaki@prit.go.jp
Watase
K
K
Yamamoto
K
K
Ogura
H
H
Yamano
M
M
Yamada
K
K
Maeno
H
H
Imaki
J
J
Kikuyama
S
S
Wada
E
E
Wada
K
K
D002001:Adipose Tissue, Brown / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure; D001835:Body Weight; D004734:Energy Metabolism; D005260:Female; D017353:Gene Deletion; D018390:Gene Targeting; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D006339:Heart Rate; D006728:Hormones / Q000097:blood; D020738:Leptin; D008297:Male; D008659:Metabolic Diseases / Q000097:blood / Q000209:etiology*; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity; D009765:Obesity / Q000097:blood / Q000209:etiology*; D011506:Proteins / Q000378:metabolism; D018004:Receptors, Bombesin / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D006728:Hormones; D020738:Leptin; D011506:Proteins; D018004:Receptors, Bombesin; C107120:bombesin receptor subtype 3; D005947:Glucose