The Gastric CB1 Receptor Modulates Ghrelin Production through the mTOR Pathway to Regulate Food Intake

Abstract

Over the years, the knowledge regarding the relevance of the cannabinoid system to the regulation of metabolism has grown steadily. A central interaction between the cannabinoid system and ghrelin has been suggested to regulate food intake. Although the stomach is the main source of ghrelin and CB1 receptor expression in the stomach has been described, little information is available regarding the possible interaction between the gastric cannabinoid and ghrelin systems in the integrated control of energy homeostasis. The main objective of the present work was to assess the functional interaction between these two systems in terms of food intake using a combination of in vivo and in vitro approaches. The present work demonstrates that the peripheral blockade of the CB1 receptor by rimonabant treatment decreased food intake but only in food-deprived animals. This anorexigenic effect is likely a consequence of decreases in gastric ghrelin secretion induced by the activation of the mTOR/S6K1 intracellular pathway in the stomach following treatment with rimonabant. In support of this supposition, animals in which the mTOR/S6K1 intracellular pathway was blocked by chronic rapamycin treatment, rimonabant had no effect on ghrelin secretion. Vagal communication may also be involved because rimonabant treatment was no longer effective when administered to animals that had undergone surgical vagotomy. In conclusion, to the best of our knowledge, the present work is the first to describe a CB1 receptor-mediated mechanism that influences gastric ghrelin secretion and food intake through the mTOR pathway.

CB1 receptor blockade counters age‐induced insulin resistance and metabolic dysfunction

“…Consequently, such a scenario may convey the apparent augmentation of rimonabant's anorectic response in older mice. Furthermore, CB1R inhibition may counteract the appetite inducing effects of peptides such as ghrelin, whose circulating levels have been shown to increase with aging in mice (Senin et al ., 2013; Lin et al ., 2014). …”

Efectos del consumo de marihuana en adultos sobre la ingesta y el metabolismo de los nutrientes: una revisión

“…Esto se debe a que la activación de los CB1 a nivel del estómago estimula la liberación de grelina 22,12 .…”

“…Se encontró que la activación del sistema cannabinoide genera un estímulo positivo sobre la ingesta de alimentos ricos en energía por parte de los individuos adictos a la marihuana ya que incide en el aumento de hormonas orexigénicas como la grelina 14,19,20 e insulina [16][17][18] , la disminución de hormonas anorexigénicas como leptina 14,15,19,20,22 y colecistoquinina 23 . Dicho estímulo orexigénico, se relaciona con una ingesta caracterizada por el consumo de alimentos palatables que a nivel nutricional podrían no ser altamente recomendados dado que suelen ser alimentos con altos contenidos de azúcares y/o grasas 21,28,30 .…”

Intestinal lipid–derived signals that sense dietary fat

“…This signaling event, which requires the efferent vagus nerve, may act as a "go" signal that promotes further eating (83,84). While the precise mechanism underlying this orexigenic response is unknown, the presence of CB 1 R in cells of the stomach that secrete ghrelin (88) and in enteroendocrine I cells that release cholecystokinin (89) suggests a possible involvement of these peptide hormones. Gut CB 1 Rs also control gastrointestinal motility (86,87,90,91) and mucosal inflammation (23).…”