Haissaguerre Magalie, Cota Daniela
Service Endocrinologie, Hôpital Haut Lévêque, CHU Bordeaux, 33600 Pessac, France.
INSERM, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U1215, 33000 Bordeaux, France - Université de Bordeaux, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U1215, 33000 Bordeaux, France.
Biol Aujourdhui. 2015;209(4):295-307. doi: 10.1051/jbio/2016009. Epub 2016 Mar 28.
The pathway of the mammalian (or mechanistic) target of rapamycin kinase (mTOR) responds to different signals such as nutrients and hormones and regulates many cellular functions as the synthesis of proteins and lipids, mitochondrial activity and the organization of the cytoskeleton. At the cellular level, mTOR forms two distinct complexes: mTORC1 and mTORC2. This review intends to summarize the various recent advances on the role of these two protein complexes in the central regulation of energy balance. mTORC1 activity modulates energy balance and metabolic responses by regulating the activity of neuronal populations, such as those located in the arcuate nucleus of the hypothalamus. Recent studies have shown that activity of the hypothalamic mTORC1 pathway varies according to cell and stimulus types, and that this signaling cascade regulates food intake and body weight in response to nutrients, such as leucine, and hormones like leptin, ghrelin and triiodothyronine. On the other hand, mTORC2 seems to be involved in the regulation of neuronal morphology and synaptic activity. However, its function in the central regulation of the energy balance is less known. Dysregulation of mTORC1 and mTORC2 is described in obesity and type 2 diabetes. Therefore, a better understanding of the molecular mechanisms involved in the regulation of energy balance by mTOR may lead to the identification of new therapeutic targets for the treatment of these metabolic pathologies.
哺乳动物雷帕霉素靶蛋白激酶（mTOR）信号通路可对营养物质和激素等不同信号作出反应，并调节多种细胞功能，如蛋白质和脂质合成、线粒体活性以及细胞骨架的组织。在细胞水平上，mTOR形成两种不同的复合物：mTORC1和mTORC2。本综述旨在总结这两种蛋白质复合物在能量平衡中枢调节中作用的最新进展。mTORC1活性通过调节神经元群体（如下丘脑弓状核中的神经元群体）的活性来调节能量平衡和代谢反应。最近的研究表明，下丘脑mTORC1信号通路的活性因细胞和刺激类型而异，并且这种信号级联反应会根据亮氨酸等营养物质以及瘦素、胃饥饿素和三碘甲状腺原氨酸等激素来调节食物摄入和体重。另一方面，mTORC2似乎参与神经元形态和突触活性的调节。然而，其在能量平衡中枢调节中的功能尚不清楚。肥胖和2型糖尿病中存在mTORC1和mTORC2的失调。因此，更好地理解mTOR调节能量平衡所涉及的分子机制可能会为这些代谢性疾病的治疗找到新的治疗靶点。
