Grupo Fisiopatología Endocrina, Instituto de Investigación Sanitaria de Santiago de Compostela, 15706 Santiago de Compostela, Spain.
CIBER Fisiopatología Obesidad y Nutrición, Instituto de Salud Carlos III, 15782 Santiago de compostela, Spain.
World J Gastroenterol. 2017 Sep 21;23(35):6403-6411. doi: 10.3748/wjg.v23.i35.6403.
To determine whether Nucb2/nesfatin1 production is regulated by the cannabinoid system through the intracellular mTOR pathway in the stomach.
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.
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.
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.
通过胃细胞内 mTOR 通路来确定大麻素系统是否调节 Nucb2/nesfatin1 的产生。
用 vehicle(对照)、rimonabant(利莫那班)、rapamycin(雷帕霉素)或 rapamycin+rimonabant 处理 Sprague Dawley 大鼠。从动物中获得胃组织,用于生化测定:实时 PCR 测量 Nucb2 mRNA,western blot 测量胃 Nucb2/nesfatin 蛋白含量,胃外植体获得胃分泌液。用酶联免疫吸附试验测量胃分泌液和血浆中的 Nucb2/nesfatin 水平。
外周注射反向激动剂,即利莫那班,抑制大麻素受体 1(CB1),减少食物摄入,增加胃分泌和循环 Nucb2/nesfatin-1 水平。此外,利莫那班处理通过增加胃组织中 pmTOR/mTOR 的表达来激活胃内 mTOR 通路,从 rimonabant 处理动物中获得的胃组织。这些作用通过使用 CB1 拮抗剂 AM281 得到了证实。当慢性用 rapamycin 处理使细胞内 mTOR/S6k 途径失活时,利莫那班处理不再能够刺激 Nucb2/nesfatin-1 的胃分泌。
外周大麻素系统通过涉及 mTOR/S6k 途径的机制调节食物摄入,该机制暗示胃产生和释放 Nucb2/Nesfatin-1。