| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2005: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Research Abstract |
Obesity is one of the most serious problems worldwide, because it is associated with lifestyle-related disease such as hypertension, cardiovascular disease and type 2 diabetes. The aims of this study are to identify novel bioactive peptides associated with regulation of energy balance and feeding behavior, and to clarify the biochemical and pathophysiological significance of the peptides.
In 2005, we identified a novel bioactive peptide, neuromedin S (NMS), in rat brain as an endogenous ligand for the G protein-coupled receptors (GPCRs) FM-3/GPR66 and FM-4/TGR-1. NMS has same core structure essential for receptor binding as anorexigenic neuropeptide, neuromedin U (NMU). Intracerebroventricular (ICV) administration of NMS in rats induced more potent suppression of feeding than that of NMU. α-MSH in the arcuate nucleus and CRH in the paraventricular nucleus were involved in NMS action on feeding. Furthermore we isolated NMS of Eurasian bombinid toads, indicating that NMS and NMU genes had already diverged at the level of the Amphibia.
Ghrelin, a novel peptide purified from stomach as an endogenous ligand for the growth hormone secretagogue receptor (GHS-R), is an acylated peptide that stimulates food intake. We showed that maternal ghrelin regulates fetal development during the late stages of pregnancy, ICV administration of des-acyl ghrelin to rats stimulates feeding through interactions with a receptor distinct from the GHS-R, and both ghrelin and des-acyl ghrelin are involved in neurogenesis of the fetal spinal cord.
In order to search for novel peptides associated with regulation of feeding behavior, we established twenty cell lines stably expressing orphan GPCRs, and developed new methods using BRET (Bioluminescence Resonance Energy Transfer) and receptor internalization.
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