Gastric Mammalian Target of Rapamycin Signaling Regulates Ghrelin Production and Food Intake
Gastric Mammalian Target of Rapamycin Signaling Regulates Ghrelin Production and Food Intake
复制标题
雷帕霉素信号传导的胃哺乳动物靶点调节生长素释放肽的产生和食物摄入
DOI：
10.1210/en.2009-0372
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发表时间：
2009-08-01
期刊：
影响因子：
4.8
通讯作者：
Zhang, Weizhen
中科院分区：
文献类型：
--
作者：
Xu, Geyang;Li, Yin;Zhang, Weizhen
胃饥饿素是一种胃激素，它向中枢神经系统提供饥饿信号以刺激食物摄入。哺乳动物雷帕霉素靶蛋白（mTOR）是细胞内能量平衡的关键传感器。在这里，我们显示了胃mTOR信号和ghrelin在能量状态变化过程中的相互关系。mTOR活性下调，而空腹胃前促生长素原和循环促生长素增加。在db/db小鼠中，胃mTOR信号增强，而胃前促生长素释放素和循环促生长素释放素减少。在野生型和db/db小鼠中，通过雷帕霉素抑制胃mTOR信号刺激胃前促生长素原和促生长素释放素mRNA的表达，并增加血浆促生长素释放素。L-亮氨酸激活胃mTOR信号降低胃前促生长素原的表达和血浆促生长素水平。过表达mTOR减弱了ghrelin启动子活性，而过表达TSC 1或TSC 2抑制mTOR活性则增加了其活性。Ghrelin受体拮抗剂D-Lys-3-GH-释放肽-6消除了雷帕霉素诱导的食物摄入增加，尽管血浆Ghrelin仍然升高。因此，mTOR是胃燃料传感器，其活性与通过胃饥饿素调节能量摄入有关。（内分泌学150：3637-3644，2009）
Ghrelin, a gastric hormone, provides a hunger signal to the central nervous system to stimulate food intake. Mammalian target of rapamycin (mTOR) is an intracellular fuel sensor critical for cellular energy homeostasis. Here we showed the reciprocal relationship of gastric mTOR signaling and ghrelin during changes in energy status. mTOR activity was down-regulated, whereas gastric preproghrelin and circulating ghrelin were increased by fasting. In db/db mice, gastric mTOR signaling was enhanced, whereas gastric preproghrelin and circulating ghrelin were decreased. Inhibition of the gastric mTOR signaling by rapamycin stimulated the expression of gastric preproghrelin and ghrelin mRNA and increased plasma ghrelin in both wild-type and db/db mice. Activation of the gastric mTOR signaling by L-leucine decreased the expression of gastric preproghrelin and the level of plasma ghrelin. Overexpression of mTOR attenuated ghrelin promoter activity, whereas inhibition of mTOR activity by overexpression of TSC1 or TSC2 increased its activity. Ghrelin receptor antagonist D-Lys-3-GH-releasing peptide-6 abolished the rapamycin-induced increment in food intake despite that plasma ghrelin remained elevated. mTOR is therefore a gastric fuel sensor whose activity is linked to the regulation of energy intake through ghrelin. (Endocrinology 150: 3637-3644, 2009)