Gastric Mammalian Target of Rapamycin Signaling Contributes to Inhibition of Ghrelin Expression Induced by Roux-En-Y Gastric Bypass
Gastric Mammalian Target of Rapamycin Signaling Contributes to Inhibition of Ghrelin Expression Induced by Roux-En-Y Gastric Bypass
复制标题
雷帕霉素信号传导的胃哺乳动物靶标有助于抑制 Roux-En-Y 胃旁路诱导的 Ghrelin 表达
DOI：
10.1159/000495325
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发表时间：
2018-11
影响因子：
--
通讯作者：
Xu Geyang
中科院分区：
文献类型：
--
作者：
Li Danjie;Li Shaojian;Pan Qinling;Zhai Hening;Peng Miao;Wang Xuanxuan;Xu Geyang
背景/目的：Roux-en-Y胃旁路手术(RYGB)是控制病态肥胖患者体重最有效的方法。RYGB能迅速改善血糖状态，减轻体重，这在很大程度上是由于包括Ghrelin在内的胃肠激素的变化。目前的研究检测了RYGB后Ghrelin合成改变的潜在机制。方法：分别测定RYGB手术前后瘦小或肥胖雄性小鼠及肥胖小鼠RYGB手术前后胃哺乳动物雷帕霉素(MTOR)信号转导靶点、Ghrelin合成和分泌情况。用Western blotting和免疫组织化学方法检测Ghrelin的表达和mTOR信号转导。实时荧光定量聚合酶链式反应检测Ghrelin基因表达水平。用酶免疫法测定血浆Ghrelin水平。结果：胃底mTOR活性明显低于前胃。禁食24小时后两者均下降。胃液中磷酸S6核糖体蛋白与Proghrelin在能量状态变化过程中呈显著负相关。在啮齿类动物和人类中，Roux-en-Y胃分流术都激活了mTOR活性，而抑制了ghrelin的表达。RYGB能显著逆转雷帕霉素诱导的瘦小鼠和肥胖小鼠Ghrelin合成增加和mTOR信号转导减弱。尾静脉注射腺病毒介导的p70核糖体蛋白亚基6激酶1(Ad-S6K1)可抑制RYGB手术小鼠与对照组相比Ghrelin的表达。结论：mTOR是一种胃燃料感受器，其活性与Roux-en-Y胃旁路术后Ghrelin的调节有关。
Background/Aims: Roux-en-Y Gastric Bypass, RYGB, is the most effective strategy to control body weight in morbid obesity. RYGB leads to rapid improvement of glycemic status and weight loss, which are largely attributed to the alteration of gastrointestinal hormones including ghrelin. The current study examined potential mechanisms of altered ghrelin synthesis after RYGB. Methods: Gastric mammalian target of rapamycin (mTOR) signaling, ghrelin synthesis and secretion were determined in lean or obese male mice with or without RYGB operation, as well as in obese patients pre- and post-RYGB surgery. Ghrelin expression and mTOR signaling were investigated by western blotting and immunohistochemistry. Ghrelin mRNA levels were detected by real-time PCR. Plasma ghrelin was measured by enzyme immunoassay. Results: mTOR activity in the gastric fundus was significantly lower than in the forestomachs. Both of them were decreased after 24h fasting. A significant negative correlation was found between gastric levels of phospho-S6 (phospho-S6 ribosomal protein) and proghrelin during changes of energy status. mTOR activity was activated, whereas ghrelin expression was inhibited by Roux-en-Y Gastric Bypass in both rodents and human beings. Increment of ghrelin synthesis and decline of mTOR signaling induced by rapamycin were significantly reversed by RYGB in both lean and obese mice. Administration of Ad-S6K1 (adenovirus-mediated p70 ribosomal protein subunit 6 kinase 1) from tail vein suppressed the expression of ghrelin in RYGB-operated mice relative to control animals. Conclusion: mTOR is therefore a gastric fuel sensor whose activity is linked to the regulation of ghrelin after Roux-en-Y Gastric Bypass.
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影响因子：
7.7
作者：
Murdolo, G;Lucidi, P;De Feo, P
通讯作者：
De Feo, P
影响因子：
4.8
作者：
Toshinai, K;Date, Y;Nakazato, M
通讯作者：
Nakazato, M
DOI：
10.1073/pnas.0502470102
发表时间：
2006-01-24
影响因子：
11.1
作者：
Doi, A;Shono, T;Nanjo, K
通讯作者：
Nanjo, K
影响因子：
5.8
作者：
Wren, AM;Seal, LJ;Bloom, SR
通讯作者：
Bloom, SR
影响因子：
5.8
作者：
Egido, EM;Rodríguez-Gallardo, J;Marco, J
通讯作者：
Marco, J