Coupling nutrient sensing to metabolic homoeostasis: the role of the mammalian target of rapamycin complex 1 pathway
Coupling nutrient sensing to metabolic homoeostasis: the role of the mammalian target of rapamycin complex 1 pathway
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DOI：
10.1017/s0029665112000754
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发表时间：
2012-11-01
影响因子：
7
通讯作者：
Cota, Daniela
中科院分区：
文献类型：
--
作者：
Andre, Caroline;Cota, Daniela
哺乳动物靶标雷帕霉素复合体1(MTORC1)途径是已知的耦合不同的环境信号来调节细胞内的几个能量需求功能，从蛋白质翻译到线粒体活动。因此，在生物体水平上，mTORC1活性通过调节在控制食物摄入量和体重方面起关键作用的神经元群的活动，以及通过决定周围组织中燃料底物的储存和使用，来影响能量平衡和一般代谢平衡。本文就mTORC1通路在能量平衡调节中的作用的研究进展作一综述。更具体地说，它旨在提供关于某些氨基酸、葡萄糖和脂肪酸影响mTORC1活性的潜在机制的知识现状，并进而说明mTORC1通路如何将营养感知与生物体能量平衡的下丘脑调节以及细胞内代谢过程的控制相结合，如葡萄糖摄取、蛋白质和脂肪的生物合成。综述的证据表明，mTORC1途径是营养物质对代谢健康作用的整合因素，并为这一细胞内途径作为治疗肥胖症和2型糖尿病等代谢性疾病的潜在靶点提供了洞察力。
The mammalian target of rapamycin complex 1 (mTORC1) pathway is known to couple different environmental cues to the regulation of several energy-demanding functions within the cell, spanning from protein translation to mitochondrial activity. As a result, at the organism level, mTORC1 activity affects energy balance and general metabolic homoeostasis by modulating both the activity of neuronal populations that play key roles in the control of food intake and body weight, as well as by determining storage and use of fuel substrates in peripheral tissues. This review focuses on recent advances made in understanding the role of the mTORC1 pathway in the regulation of energy balance. More particularly, it aims at providing an overview of the status of knowledge regarding the mechanisms underlying the ability of certain amino acids, glucose and fatty acids, to affect mTORC1 activity and in turn illustrates how the mTORC1 pathway couples nutrient sensing to the hypothalamic regulation of the organisms' energy homoeostasis and to the control of intracellular metabolic processes, such as glucose uptake, protein and lipid biosynthesis. The evidence reviewed pinpoints the mTORC1 pathway as an integrator of the actions of nutrients on metabolic health and provides insight into the relevance of this intracellular pathway as a potential target for the therapy of metabolic diseases such as obesity and type-2 diabetes.