演題詳細
Poster
代謝、摂食調節
Metabolism and Regulation of Food Intake
開催日 | 2014/9/13 |
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時間 | 11:00 - 12:00 |
会場 | Poster / Exhibition(Event Hall B) |
マウス視床下部腹内側におけるレプチン受容体、コレシストキニン受容体間の機能的相乗作用
Functional synergy between cholecystokinin 1 receptors and leptin receptors in the murine ventromedial hypothalamus
- P3-197
- 竹内 公平 / Kouhei Takeuchi:1 池田 真行 / masayuki ikeda:1,2 Mohammad Shahid / Shahid Mohammad:1 片岡 絢 / aya kataoka:2 金 主賢 / Juhyon kim:1,2 瀧口 総一 / Soichi takiguchi:3
- 1:富山大学大学院・生命融合科学 / Dept innovative life science, Postgraduate school, Toyama, Japan 2:富山大学大学院・理工学 / Dept science and engineering 3:九州がんセンター / National Kyushu Cancer Center
Cholecystokinin (CCK) and leptin are both satiety-controlling signaling peptides yet their functional coupling at the levels of hypothalamus is obscure. Thus, we analyzed gene-expression profiles of leptin receptor (ObR-b) in the hypothetical satiety controlling centers using a real time RT-PCR. The results indicated ObR-b over-expression in the ventromedial hypothalamus (VMH) in knockout mice lacking CCK-1 receptors (CCK1R-/-). Fura-2 based cytosolic Ca2+ imaging using acutely isolated hypothalamic slices also demonstrated that CCK-1 receptor agonist (CCK-8s) up-regulated whereas CCK-1 receptor antagonist (lorglumide) down-regulated leptin-induced Ca2+ mobilizations in the VMH. These effects of CCK-8s and lorglumide were absent in CCK1R-/- slices, confirming their actions via CCK-1 receptors. In addition, current clamp recordings demonstrated that CCK-8s and leptin additively activated action potential firings in the wild type VMH neurons. Furthermore, western blot analysis indicated that CCK-8s promoted leptin-induced STAT3 phosphorylation in the hypothalamic slices of wild type but not of CCK1R-/-. Based on these lines of evidences, we conclude that CCK-1 receptor contributes to leptin receptor signaling in VMH neurons and suggest a synergistic interaction of CCK and leptin signaling for the regulation of satiety in the hypothalamus.