[Role of the mTOR pathway in the central regulation of energy balance].

M. Haissaguerre, D. Cota
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Abstract

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.
[mTOR通路在能量平衡中枢调节中的作用]。
雷帕霉素激酶(mTOR)的哺乳动物(或机制)靶点通路响应不同的信号,如营养物质和激素,并调节许多细胞功能,如蛋白质和脂质的合成,线粒体活性和细胞骨架的组织。在细胞水平上,mTOR形成两种不同的复合物:mTORC1和mTORC2。本文就这两种蛋白复合物在能量平衡中枢调控中的作用的最新研究进展作一综述。mTORC1活性通过调节神经元群的活动来调节能量平衡和代谢反应,例如位于下丘脑弓状核的神经元群。最近的研究表明,下丘脑mTORC1通路的活性根据细胞和刺激类型而变化,该信号级联调节食物摄入和体重,以响应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。另一方面,mTORC2似乎参与神经元形态和突触活动的调节。然而,其在能量平衡中枢调节中的作用却鲜为人知。mTORC1和mTORC2的失调在肥胖和2型糖尿病中被描述。因此,更好地了解mTOR调节能量平衡的分子机制可能有助于发现治疗这些代谢病理的新靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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