A Selective Bombesin Receptor Subtype 3 Agonist Promotes Weight Loss in Diet-Induced–Obese Rats With Circadian Rhythm Change
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- Nio Yasunori
- 武田薬品工業再生医療ユニットOrganoid medicine PJ
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- Maruyama Minoru
- 武田薬品工業㈱CNS drug discovery unit
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- Hotta Natsu
- 武田薬品工業㈱CNS drug discovery unit
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- Nagisa Yasutaka
- 武田薬品工業㈱Japan Medical Affairs
Bibliographic Information
- Other Title
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- 新規選択的ボンベシンサブタイプ3受容体アゴニストは脳-肝リズムを変化させて抗肥満作用を示す。
Description
<p>Bombesin receptor subtype 3 (BRS-3) is an orphan G protein–coupled receptor. Based on the obese phenotype of male BRS-3–deficient mice, BRS-3 has been considered an attractive target for obesity treatment. Here, we developed a novel selective BRS-3 agonist (compound-A) and evaluated its antiobesity effects. Compound-A showed anorectic effects and enhanced energy expenditure in dietinduced–obese (DIO)-F344 rats. Moreover, repeated oral administration of compound-A for 7 days resulted in a significant body weight reduction in DIO-F344 rats. To investigate the underlying mechanisms of BRS-3 agonist effects, we focused on the suprachiasmatic nucleus (SCN), the main control center of circadian rhythms in the hypothalamus, also regulating sympathetic nervous system. Compound-A significantly increased the messenger RNA expression of Brs-3, c-fos, and circadian rhythm genes in SCN of DIO-F344 rats. On this basis, energy expenditure enhancement by compound-A may be due to a circadian rhythm change in central and peripheral tissues, enhancement of peripheral lipid metabolism, and stimulation of the sympathetic nervous system. According to these results, BRS-3 agonist might be a good option for obesity treatment with circadian rhythm change and increase of energy expenditure.</p>
Journal
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- Proceedings for Annual Meeting of The Japanese Pharmacological Society
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Proceedings for Annual Meeting of The Japanese Pharmacological Society 92 (0), 1-YIA-21-, 2019
Japanese Pharmacological Society
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Details 詳細情報について
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- CRID
- 1390846609814456192
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- NII Article ID
- 130007812881
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- ISSN
- 24354953
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- Text Lang
- ja
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- Data Source
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- JaLC
- Crossref
- CiNii Articles
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- Abstract License Flag
- Disallowed