Gastroenterology

Gastroenterology

Volume 116, Issue 6, June 1999, Pages 1287-1292
Gastroenterology

Rapid Communications
Urocortin reduces food intake and gastric emptying in lean and ob/ob obese mice,☆☆

https://doi.org/10.1016/S0016-5085(99)70491-9Get rights and content

Abstract

Background & Aims: Gastric emptying plays an important role in regulating food intake. This study was designed to investigate whether intraperitoneally injected urocortin reduces gastric emptying, feeding, and body weight in lean and ob/ob obese mice. Methods: Food intake and body weight were measured after intraperitoneal injections of one of the following: urocortin, deamidated form of urocortin (urocortin OH), corticotropin-releasing factor (CRF), CRF6-33, cholecystokinin octapeptide (CCK-8), and leptin in 16-hour food-deprived animals. Gastric emptying was assessed 2, 4, or 8 hours after intraperitoneal injection. Repeated injections of urocortin were continued for 5 days in ob/ob mice. Results: Urocortin (0.003-3 nmol) dose-dependently and potently decreased food intake and body weight gain in lean mice. The ranking order of potency was urocortin > urocortin OH ≥ CRF > CCK-8 > CRF6-33 > leptin. Gastric emptying was also potently reduced by urocortin with a similar ranking order of potency of urocortin > CRF > urocortin OH > CCK-8. Simultaneous administration of urocortin and CRF receptor antagonist, α-helical CRF9-41, blocked the effects of urocortin. Urocortin reduced food intake and body weight gain, as well as the rate of gastric emptying, in ob/ob mice, which was significantly faster than that of lean mice. Five daily injections of urocortin significantly lowered body weight and improved glycemic control in ob/ob mice. Conclusions: The urocortin-induced decrease in food intake and body weight in lean and ob/ob mice is closely related to gastric emptying and opens new possibilities for the treatment of obesity.

GASTROENTEROLOGY 1999;116:1287-1292

Section snippets

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).

. Effects of 0.003-3 nmol of urocortin injected IP on (A) cumulative food intake

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.

References (21)

There are more references available in the full text version of this article.

Cited by (0)

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.

☆☆

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.).

View full text