Interaction between the ghrelin and CCK1 receptors and its effect on meal patterns.

Abstract

Food intake is regulated by signals coming from the gastrointestinal (GI) tract and by the brain. The GI peptides ghrelin and cholecystokinin (CCK) exert opposite effects on ingestive behavior and CCK may modulate the orexigenic effects of ghrelin. We have previously observed that CCK type 1 receptor null mice (CCK1R-/-) eat larger meals and eat sooner after a 6 h fast compared to their wildtype (WT) counterparts. In the present study, we determined the role of the ghrelin receptor in the orexigenic response in CCK-/- mice. CCK1R-/- and CCK1R+/+ mice ( n =8) were fed isocaloric high-fat (HF) or low-fat (LF) diets for 2 weeks and meal pattern analysis was performed. Administration of the ghrelin receptor antagonist d -[Lys]-GHRP-6 (200 nmol ip, 15 min) decreased the size of the first meal by 54% in CCK1R-/- fed HF diet ( p <0.01) and increased the time to the first meal in CCK1R-/- fed either LF or HF diet (time to first meal, secs: HF: 27±10 vs. 1055±399 p <0.001; LF: 121±39 vs. 315±139, p <0.01). The ghrelin receptor antagonist had no effect on meal duration, intermeal interval or meal frequency in any group. These results indicate that ghrelin and CCK1 receptors act in coordination to regulate short-term food intake. These data suggest that, in the absence of the CCK1R, ghrelin determines the timing and size of the first meal.