Urocrotin reduces food intake and gastric emptying in lean and ob/ob obesemice

Background & Aims: Gastric emptying plays an important role in regulating f ood intake. This study was designed to investigate whether intraperitoneall y injected urocortin reduces gastric emptying, feeding, and body weight in lean and ob/ob obese mice. Methods: Food intake and body weight were measur ed after intraperitoneal injections of one of the following: urocortin, dea midated form of urocortin (urocortin OH), corticotropin-releasing factor (C RF), CRF6-33, cholecystokinin octapeptide (CCK-8), and leptin in 16-hour fo od-deprived animals. Gastric emptying was assessed 2, 4, or 8 hours after i ntraperitoneal injection. Repeated injections of urocortin were continued f or 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 greater than or equal to CRF > CCK-8 > CRF6-33 > leptin. Gastric emptying was also potently redu ced by urocortin with a similar ranking order of potency of urocortin > CRF > urocortin OH > CCK-8. Simultaneous administration of urocortin and CRF r eceptor antagonist, alpha-helical CRF9-41, blocked the effects of urocortin . Urocortin reduced food intake and body weight gain, as well as the rate o f gastric emptying, in ob/ob mice, which was significantly faster than that of lean mice. Five daily injections of urocortin significantly lowered bod y weight and improved glycemic control in ob/ob mice. Conclusions: The uroc ortin-induced decrease in food intake and body weight in lean and ob/ob mic e is closely related to gastric emptying and opens new possibilities for th e treatment of obesity.