AIM To determine whether Nucb2/nesfatin1 production is regulated by the cannabinoid system through the intracellular m TOR pathway in the stomach.METHODS Sprague Dawley rats were treated with vehicle,rimonabant,rapamy...AIM To determine whether Nucb2/nesfatin1 production is regulated by the cannabinoid system through the intracellular m TOR 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 m RNA 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 m TOR pathway in the stomach as showed by the increase in pm TOR/m TOR 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 m TOR/S6 k 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 m TOR/S6 k pathway.展开更多
基金Supported by Instituto de Salud Carlos III,No.PI15/01272 cofounded by FEDERFondo de Investigaciones Sanitarias(LS:I3SNS-SERGAS/ISCIII)Centro de Investigacion Biomedica en Red Fisiopatología de la Obesidad y Nutrición(CIBERobn)is a iniciative of the Instituto de Salud Carlos III(ISCIII)of Spain which is supported by FEDER funds
文摘AIM To determine whether Nucb2/nesfatin1 production is regulated by the cannabinoid system through the intracellular m TOR 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 m RNA 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 m TOR pathway in the stomach as showed by the increase in pm TOR/m TOR 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 m TOR/S6 k 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 m TOR/S6 k pathway.
