RT Journal Article T1 Ghrelin-induced orexigenic effect in rats depends on the metabolic status and is counteracted by peripheral CB1 receptor antagonism. A1 Alen, Francisco A1 Crespo, Inmaculada A1 Ramírez-López, María Teresa A1 Jagerovic, Nadine A1 Goya, Pilar A1 Rodríguez de Fonseca, Fernando A1 Gómez de Heras, Raquel A1 Orio, Laura K1 Animales K1 Ghrelina K1 Masculino K1 Piperidinas K1 Ratas K1 Ratas Wistar K1 Ingestión de Alimentos K1 Receptor cannabinoide CB1 AB Ghrelin is an endogenous regulator of energy homeostasis synthesized by the stomach to stimulate appetite and positive energy balance. Similarly, the endocannabinoid system is part of our internal machinery controlling food intake and energy expenditure. Both peripheral and central mechanisms regulate CB1-mediated control of food intake and a functional relationship between hypothalamic ghrelin and cannabinoid CB1 receptor has been proposed. First of all, we investigated brain ghrelin actions on food intake in rats with different metabolic status (negative or equilibrate energy balance). Secondly, we tested a sub-anxiogenic ultra-low dose of the CB1 antagonist SR141716A (Rimonabant) and the peripheral-acting CB1 antagonist LH-21 on ghrelin orexigenic actions. We found that: 1) central administration of ghrelin promotes food intake in free feeding animals but not in 24 h food-deprived or chronically food-restricted animals; 2) an ultra-low dose of SR141716A (a subthreshold dose 75 folds lower than the EC50 for induction of anxiety) completely counteracts the orexigenic actions of central ghrelin in free feeding animals; 3) the peripheral-restricted CB1 antagonist LH-21 blocks ghrelin-induced hyperphagia in free feeding animals. Our study highlights the importance of the animaĺs metabolic status for the effectiveness of ghrelin in promoting feeding, and suggests that the peripheral endocannabinoid system may interact with ghrelińs signal in the control of food intake under equilibrate energy balance conditions. PB Public Library of Science YR 2013 FD 2013-04-02 LK http://hdl.handle.net/10668/1419 UL http://hdl.handle.net/10668/1419 LA en NO Alen F, Crespo I, Ramírez-López MT, Jagerovic N, Goya P, de Fonseca FR, et al. Ghrelin-induced orexigenic effect in rats depends on the metabolic status and is counteracted by peripheral CB1 receptor antagonism. PLoS ONE. 2013; 8(4):e60918 NO Journal Article; Research Support, Non-U.S. Gov't; DS RISalud RD Apr 8, 2025