Department of Genetics & Complex Diseases, Harvard School of Public Health, 665 Huntington Avenue, SPH2-117, Boston, Massachusetts 02115, USA.
EMBO Rep. 2013 Mar 1;14(3):242-51. doi: 10.1038/embor.2013.5. Epub 2012 Feb 12.
The mechanistic target of rapamycin is a protein kinase that, as part of the mechanistic target of rapamycin complex 1 (mTORC1), senses both local nutrients and, through insulin signalling, systemic nutrients to control a myriad of cellular processes. Although roles for mTORC1 in promoting protein synthesis and inhibiting autophagy in response to nutrients have been well established, it is emerging as a central regulator of lipid homeostasis. Here, we discuss the growing genetic and pharmacological evidence demonstrating the functional importance of its signalling in controlling mammalian lipid metabolism, including lipid synthesis, oxidation, transport, storage and lipolysis, as well as adipocyte differentiation and function. Defining the role of mTORC1 signalling in these metabolic processes is crucial to understanding the pathophysiology of obesity and its relationship to complex diseases, including diabetes and cancer.
雷帕霉素的作用靶点是一种蛋白激酶,作为雷帕霉素靶蛋白复合物 1(mTORC1)的一部分,它可以感知局部营养素,并通过胰岛素信号传递系统营养素,从而控制多种细胞过程。虽然 mTORC1 在响应营养素时促进蛋白质合成和抑制自噬的作用已得到充分证实,但它正逐渐成为脂质稳态的中央调节剂。在这里,我们讨论了越来越多的遗传和药理学证据,这些证据表明其信号在控制哺乳动物脂质代谢中的功能重要性,包括脂质合成、氧化、运输、储存和脂肪分解,以及脂肪细胞分化和功能。确定 mTORC1 信号在这些代谢过程中的作用对于理解肥胖症的病理生理学及其与复杂疾病(包括糖尿病和癌症)的关系至关重要。