Chronic central administration of ghrelin reverses the effects of leptin

OBJECTIVE: To determine whether chronic central administration of ghrelin can block the effects of leptin on food intake, adiposity, and plasma concentrations of metabolic parameters and hormones. DESIGN: Intracerebroventricular (ICV) infusions of leptin (5 mg/day) for 7 days, with or without ghrelin (1.2 mug/day), in rats. Rats administered leptin plus ghrelin were divided into ad lib-fed and food-restricted groups. MEASUREMENT: Body weight and food intake were monitored daily. Following killing on day 8, epididymal fat weight and fasting plasma concentrations of glucose, insulin, leptin, ghrelin, IGF-1, and adiponectin were determined. RESULTS: ICV infusion of leptin decreased food intake by 39% and fat weight by 41%. Leptin decreased plasma concentrations of glucose, insulin, and leptin and increased plasma ghrelin levels. Central coadministration of ghrelin blocked the effects of leptin. Most of the effects of ghrelin were diminished by food restriction but ghrelin effect on adiposity and plasma insulin concentrations remained in food-restricted rats. CONCLUSION: Chronic central administration of ghrelin reversed the effects of leptin, primarily by altering food intake, but ghrelin may have regulatory effects on adiposity and plasma insulin levels independent of feeding effect.