mTOR信号通路对脂肪生成的调控作用

The Regulation of mTOR Signaling Pathway on Adipogenesis

脂肪组织是一种主要的能量储存和内分泌器官。脂肪生成是一系列复杂的细胞分化过程,受到细胞营养水平、激素和代谢物等调节。哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)复合物包括哺乳动物雷帕霉素靶蛋白复合体1(mammalian target of rapamycin complex 1,mTORC1)和mTORC2两种蛋白质复合体。mTOR复合物含有的脂质激酶样域奠定了mTOR通路调控脂肪生成的基础。对mTORC1和mTORC2的部分组成蛋白质研究也验证了mTOR调控成脂的功能。基于前期的研究,我们综述了miR-199a-3p、miR-103、miR-188、68 kD有丝分裂中的Src相关底物(Src-associated substrate in mitosis of 68 kD,Sam68)、内皮抑素等物质通过mTORC1和mTORC2蛋白质复合体调控脂肪生成的机制。同时,进一步构建了包括胰岛素/IGF通路、PI3K-AKT通路、氨基酸通路、AMPK通路、cAMP通路、cGMP通路、NOTCH通路以及影响上述通路的bta-miR-150、4-O-甲基蔗糖和多种蛋白质在内的mTOR信号通路调控脂肪生成的网络。本文主要综述了mTOR复合物的特性和mTOR通路调控脂肪生成方面的最新研究进展,指出mTORC2具有调控脂质摄取和脂质分解的作用,调控mTORC1功能的作用,但是有关mTORC2的研究相对mTORC1较少,因此,对脂肪生成和脂质代谢的进一步研究需要集中于mTORC2。

Adipose tissue is a major energy storage and endocrine organ.Adipogenesis is a complex process of cell differentiation,which is regulated by nutrient levels,hormones and metabolites,etc.The mammalian target of rapamycin(mTOR)complex includes two protein complexes,mammalian target of rapamycin complex 1(mTORC1)and mTORC2.The lipid kinase-like domain contained in the mTOR complex lays the foundation for the mTOR pathway to regulate adipogenesis.Research on some components of mTORC1 and mTORC2 has verified the roles of mTOR in the regulation of adipogenesis.Based on previous studies,we reviewed the research of miR-199 a-3 p,miR-103,miR-188,Src-associated substrate in mitosis of 68 kD(Sam68),endostatin and other substances in the regulation of adipogenesis through mTORC1 and mTORC2.At the same time,we had further constructed the adipogenesis network regulated by mTOR signaling pathway,including insulin/IGF pathway,PI3 K-AKT pathway,amino acid pathway,AMPK pathway,cAMP pathway,cGMP pathway,NOTCH pathway,and the modulation of bta-miR-150,4-O-methylasochlorin and a variety of proteins.This article mainly reviewed the characteristics of mTOR complex and the latest research progress in the regulation of adipogenesis by mTOR pathway.It was pointed out that mTORC2 can regulate lipid uptake,lipolysis and regulate the function of mTORC1.However,there are fewer studies on mTORC2 compared to mTORC1,so further researches on adipogenesis and lipid metabolism may be more focused on mTORC2.