mTOR-dependent Modulation of Gastric Nesfatin-1/NUCB2
mTOR-dependent Modulation of Gastric Nesfatin-1/NUCB2
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mTOR 依赖性胃 Nesfatin-1/NUCB2 调节
DOI：
10.1159/000338503
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发表时间：
2012-01-01
影响因子：
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通讯作者：
Zhang, Weizhen
中科院分区：
文献类型：
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作者：
Li, Ziru;Xu, Geyang;Zhang, Weizhen
背景：Nesfatin-1是一种由核结合素前体素2(nubindin-2，NUCB2)衍生的82个氨基酸的多肽，是一种通过瘦素非依赖机制作用于下丘脑的新的饱腹感激素。Nesfatin-1/NUCB2的产生受到调控的机制尚不清楚。方法：采用逆转录聚合酶链式反应和免疫荧光染色或Western blotting方法检测胃组织和Min-6细胞中Nesfatin-1/NUCB2的mRNA和免疫反应性。结果：Nesfatin-1/NUCB2与哺乳动物雷帕霉素靶基因(MTOR)下游靶点pS6K1共定位于胃X/A样细胞。在能量状态变化过程中，胃mTOR信号与Nesfatin-1/NUCB2之间存在平行关系。禁食后mTOR活性和胃内Nesfatin-1/NUCB2均下调，重新喂养后恢复到基础水平。在高脂饮食诱导的肥胖小鼠，胃mTOR信号和Nesfatin-1/NUCB2增加。雷帕霉素抑制胃mTOR信号转导通路可减弱瘦小鼠和肥胖小鼠胃组织中Nesfatin-1/NUCB2基因和蛋白的表达。雷帕霉素对mTOR活性的抑制或TSC1或TSC2的过表达降低了Min-6细胞中Nesfatin-1/NUCB2的表达，提示mTOR信号的直接作用。结论：胃mTOR是一种胃能量感受器，其活性与胃Nesfatin-1/NUCB2的调节有关。
Background: Nesfatin-1, an 82 amino acid peptide derived from the prohormone nucleobindin-2 (NUCB2), is a novel satiety hormone acting through a leptin-independent mechanism in the hypothalamus. The mechanisms by which production of nesfatin-1/NUCB2 is regulated remain unknown. Methods: Nesfatin-1/NUCB2 mRNA and immunoreactivity were examined in gastric tissue and Min-6 cells by RT-PCR and immunofluorescent staining or Western blotting. Results: Nesfatin-1/NUCB2 is co-localized with pS6K1, the downstream target of mammalian target of rapamycin (mTOR), in gastric X/A like cells. A parallel relationship between gastric mTOR signaling and nesfatin-1/NUCB2 was observed during changes in energy status. Both mTOR activity and gastric nesfatin-1/NUCB2 were down-regulated by fasting, and returned to basal levels with re-feeding. In high fat diet induced obese mice, gastric mTOR signaling and nesfatin-1/NUCB2 were increased. Inhibition of the gastric mTOR signaling by rapamycin attenuated the expression of gastric nesfatin-1/NUCB2 mRNA and protein in both lean and obese mice. Attenuation of mTOR activity by rapamycin or over-expression of TSC1 or TSC2 reduced the expression of nesfatin-1/NUCB2 in Min-6 cells, suggesting a direct effect of mTOR signaling. Conclusion: Gastric mTOR is a gastric energy sensor whose activity is linked to the regulation of gastric nesfatin-1/NUCB2.