title: 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.
authors.affiliation: Grupo Fisiopatologia Endocrina, Instituto de Investigacion Sanitaria de Santiago de Compostela (IDIS), Complexo Hospitalario Universitario de Santiago (CHUS/SERGAS), Santiago de Compostela, Spain ; CIBER Fisiopatologia Obesidad y Nutricion (CB06/03), Instituto de Salud Carlos III, Santiago de Compostela, Spain.
authors.forename: Lucia L
authors.initials: LL
authors.lastname: Senin
authors.forename: Omar
authors.initials: O
authors.lastname: Al-Massadi
authors.forename: Cintia
authors.initials: C
authors.lastname: Folgueira
authors.forename: Cecilia
authors.initials: C
authors.lastname: Castelao
authors.forename: Maria
authors.initials: M
authors.lastname: Pardo
authors.forename: Silvia
authors.initials: S
authors.lastname: Barja-Fernandez
authors.forename: Arturo
authors.initials: A
authors.lastname: Roca-Rivada
authors.forename: Maria
authors.initials: M
authors.lastname: Amil
authors.forename: Ana B
authors.initials: AB
authors.lastname: Crujeiras
authors.forename: Tomas
authors.initials: T
authors.lastname: Garcia-Caballero
authors.forename: Enrico
authors.initials: E
authors.lastname: Gabellieri
authors.forename: Rosaura
authors.initials: R
authors.lastname: Leis
authors.forename: Carlos
authors.initials: C
authors.lastname: Dieguez
authors.forename: Uberto
authors.initials: U
authors.lastname: Pagotto
authors.forename: Felipe F
authors.initials: FF
authors.lastname: Casanueva
authors.forename: Luisa M
authors.initials: LM
authors.lastname: Seoane
mesh_terms: D000818:Animals; D002186:Cannabinoids / Q000378:metabolism / Q000494:pharmacology; D005247:Feeding Behavior; D005753:Gastric Mucosa / Q000378:metabolism; D015870:Gene Expression; D054439:Ghrelin / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics / Q000494:pharmacology; D007150:Immunohistochemistry; D008297:Male; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000077285:Rimonabant; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D002186:Cannabinoids; D054439:Ghrelin; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D058570:TOR Serine-Threonine Kinases; D000077285:Rimonabant