Pharmacological inhibition of cannabinoid receptor 1 stimulates gastric release of nesfatin-1 via the mTOR pathway

Cintia Folgueira, Silvia Barja-Fernandez, Laura Prado, Omar Al-Massadi, Cecilia Castelao, Veronica Pena-Leon, Patricia Gonzalez-Saenz, Javier Baltar, Ivan Baamonde, Rosaura Leis, Carlos Dieguez, Uberto Pagotto, Felipe F. Casanueva, Sulay A. Tovar, Ruben Nogueiras, Luisa M. Seoane

Research output: Indexed journal article Articlepeer-review

9 Citations (Scopus)

Abstract

AIM To determine whether Nucb2/nesfatin1 production is regulated by the cannabinoid system through the intracellular mTOR pathway in the stomach. METHODS Sprague Dawley rats were treated with vehicle, rimonabant, rapamycin or rapamycin+rimonabant. Gastric tissue obtained from the animals was used for biochemical assays: Nucb2 mRNA measurement by real time PCR, gastric Nucb2/nesfatin protein content by western blot, and gastric explants to obtain gastric secretomes. Nucb2/nesfatin levels were measured in gastric secretomes and plasma using enzyme-linked immunosorbent assay. RESULTS The inhibition of cannabinoid receptor 1 (CB1) by the peripheral injection of an inverse agonist, namely rimonabant, decreases food intake and increases the gastric secretion and circulating levels of Nucb2/nesfatin-1. In addition, rimonabant treatment activates mTOR pathway in the stomach as showed by the increase in pmTOR/mTOR expression in gastric tissue obtained from rimonabant treated animals. These effects were confirmed by the use of a CB1 antagonist, AM281. When the intracellular pathway mTOR/S6k was inactivated by chronic treatment with rapamycin, rimonabant treatment was no longer able to stimulate the gastric secretion of Nucb2/nesfatin-1. CONCLUSION The peripheral cannabinoid system regulates food intake through a mechanism that implies gastric production and release of Nucb2/Nesfatin-1, which is mediated by the mTOR/S6k pathway.

Original languageEnglish
Pages (from-to)6403-6411
Number of pages9
JournalWorld Journal of Gastroenterology
Volume23
Issue number35
DOIs
Publication statusPublished - 21 Sept 2017
Externally publishedYes

Keywords

  • Cannabinoid receptor 1
  • Food intake
  • mTOR
  • NUCB2/nesfatin-1
  • Stomach

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