Rapid CommunicationsUrocortin reduces food intake and gastric emptying in lean and ob/ob obese mice☆,☆☆
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Materials and methods
Male mice (32-35 g) of the ddy strain were purchased from JAPAN SLC (Shizuoka, Japan) at 7 weeks of age. Obese (ob/ob) C57BL/6J mice (38-42 g) were obtained from Shionogi Co., Ltd. (Shiga, Japan) at 10-11 weeks of age. They were housed individually in a regulated environment (22 ± 2°C, 55% ± 10% humidity, 12/12-hour light/dark cycle with light on at 7 AM). Food and water were available ad libitum except when otherwise indicated. The mice were used only once each in the experiment. All
Food intake and body weight after an acute IP injection of peptides in lean mice
We examined the effects of a single IP injection of urocortin (0.003-3 nmol/mouse) on food intake and body weight over a 96-hour period in 16-hour fasted lean mice with comparison to CRF, CRF6-33, and urocortin OH, as well as leptin and CCK-8. Urocortin potently and significantly reduced the cumulative food intake after a 20-minute period compared with the saline control group in a dose-related manner (Figure 1A).
Discussion
Physiological mechanisms regulating food intake and body weight are complex and remain to be determined. However, leptin, a hormone secreted by adipose tissue, was found to be an integral component of this system.9, 11 Until now, several peptides were thought to decrease food intake, including CRF and CCK-8, which modulate meal patterns (hunger and/or satiety).13 Previous studies have shown that centrally administered urocortin dose-dependently produced a more potent suppression of food intake
Acknowledgements
The authors thank Dr. Tokio Yamaguchi (Drug Discovery Laboratory, Yamanouchi Pharmaceutical Co., Ltd.) for performing 125I-sauvagine binding to cloned CRF type 1 and type 2 receptors.
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Address requests for reprints to: Akio Inui, M.D., Ph.D., Second Department of Internal Medicine, Kobe University School of Medicine, Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan. e-mail: [email protected]; fax: (81) 78-382-2080.
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Supported in part by Grants-in-Aid for Scientific Research (no. 09671057), Developmental Scientific Research (no. 08559012), and International Scientific Research (no. 80168418) from The Ministry of Education, Science, Sports, and Culture of Japan (to A.I.).