Hypothalamic mTOR signaling regulates food intake
Hypothalamic mTOR signaling regulates food intake
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DOI：
10.1126/science.1124147
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发表时间：
2006-05-12
期刊：
影响因子：
56.9
通讯作者：
Seeley, RJ
中科院分区：
文献类型：
--
作者：
Cota, D;Proulx, K;Seeley, RJ
哺乳动物雷帕霉素靶蛋白（mTOR）是一种丝氨酸-苏氨酸激酶，通过感知能量状态的变化来调节细胞周期进程和生长。我们证明了mTOR信号传导在响应营养可用性的大脑机制中发挥作用，调节能量平衡。在大鼠中，mTOR信号传导受下丘脑特定区域的能量状态控制，并与弓状核中的神经肽Y和阿黑皮素原神经元共定位。亮氨酸的中枢给药增加下丘脑mTOR信号传导并减少食物摄入和体重。激素瘦素增加下丘脑mTOR活性，而mTOR信号传导的抑制会减弱瘦素的厌食作用。因此，mTOR是一种细胞燃料传感器，其下丘脑活动直接与能量摄入的调节有关。
The mammalian Target of Rapamycin ( mTOR) protein is a serine-threonine kinase that regulates cell-cycle progression and growth by sensing changes in energy status. We demonstrated that mTOR signaling plays a role in the brain mechanisms that respond to nutrient availability, regulating energy balance. In the rat, mTOR signaling is controlled by energy status in specific regions of the hypothalamus and colocalizes with neuropeptide Y and proopiomelanocortin neurons in the arcuate nucleus. Central administration of leucine increases hypothalamic mTOR signaling and decreases food intake and body weight. The hormone leptin increases hypothalamic mTOR activity, and the inhibition of mTOR signaling blunts leptin's anorectic effect. Thus, mTOR is a cellular fuel sensor whose hypothalamic activity is directly tied to the regulation of energy intake.