Li Ziru, Xu Geyang, Li Yin, Zhao Jing, Mulholland Michael W, Zhang Weizhen
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing, China.
Cell Physiol Biochem. 2012;29(3-4):493-500. doi: 10.1159/000338503. Epub 2012 Apr 3.
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.
Nesfatin-1/NUCB2 mRNA and immunoreactivity were examined in gastric tissue and Min-6 cells by RT-PCR and immunofluorescent staining or Western blotting.
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.
Gastric mTOR is a gastric energy sensor whose activity is linked to the regulation of gastric nesfatin-1/NUCB2.
Nesfatin-1是一种由前激素核结合蛋白-2（NUCB2）衍生而来的含82个氨基酸的肽，是一种新型的饱腹感激素，通过下丘脑内不依赖瘦素的机制发挥作用。Nesfatin-1/NUCB2产生的调节机制尚不清楚。
通过逆转录聚合酶链反应（RT-PCR）以及免疫荧光染色或蛋白质免疫印迹法检测胃组织和Min-6细胞中的Nesfatin-1/NUCB2信使核糖核酸（mRNA）和免疫反应性。
在胃X/A样细胞中，Nesfatin-1/NUCB2与哺乳动物雷帕霉素靶蛋白（mTOR）的下游靶点pS6K1共定位。在能量状态变化期间，观察到胃mTOR信号传导与Nesfatin-1/NUCB2之间存在平行关系。禁食会下调mTOR活性和胃Nesfatin-1/NUCB2，重新进食后恢复至基础水平。在高脂饮食诱导的肥胖小鼠中，胃mTOR信号传导和Nesfatin-1/NUCB2增加。雷帕霉素抑制胃mTOR信号传导可减弱瘦小鼠和肥胖小鼠胃Nesfatin-1/NUCB2 mRNA和蛋白质的表达。雷帕霉素抑制mTOR活性或过表达结节性硬化症复合物1（TSC1）或结节性硬化症复合物2（TSC2）可降低Min-6细胞中Nesfatin-1/NUCB2的表达，提示mTOR信号传导具有直接作用。
胃mTOR是一种胃能量传感器，其活性与胃Nesfatin-1/NUCB2的调节有关。
