Research Progress of mTOR Signaling Pathway in Metabolic Diseases
Journal: Journal of Clinical Medicine Research DOI: 10.32629/jcmr.v6i4.4804
Abstract
Mammalian target of rapamycin (mTOR) is a highly conserved central regulator within cells. It integrates signals from various inputs, including nutrients, energy status, and growth factors, to precisely regulate fundamental cellular processes such as cell growth, proliferation, autophagy, and metabolism through multiple signaling pathways. In recent years, numerous studies have confirmed that the abnormal activation of the mTOR signaling pathway is closely associated with the occurrence and progression of various metabolic diseases. This article aims to summarize the research progress on the mTOR signaling pathway in metabolic diseases such as obesity, type 2 diabetes mellitus, hyperuricemia, and osteoporosis, explore its molecular mechanisms, and provide an outlook on therapeutic strategies targeting mTOR.
Keywords
mTOR; metabolic diseases; obesity; type 2 diabetes mellitus; hyperuricemia; osteoporosis.
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[4] SUN K, KUSMINSKI C M. Adipose tissue remodeling in obesity: mechanisms and therapeutic targets [J].Bioengineering & Translational Medicine, 2025, 10(1): e12500.
[5] Zhang Y, Fang X, Wei J, et al. Adipose-specific mTORC1 deficiency attenuates high-fat diet-induced obesity and insulin resistance in mice[J]. Diabetes, 2021, 70(10): 2252-2264.
[6] Wang S, Liang X, Yang Q, et al. mTORC1 suppresses beige adipose tissue thermogenesis via phosphorylation of AKT1-mediated HDAC1/2[J]. Nature Communications, 2022, 13: 634.
[7] Campos C, Flores-Opazo M, Valladares-Ide D, et al. Fiber-specific differences in protein content of pathways related to mTORC1 signaling and oxidative metabolism in individuals with obesity. Sci Rep. 2025 Jul 4;15(1):23839. doi: 10.1038/s41598-025-09169-7. PMID: 40610657; PMCID: PMC12229446.
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[11] Krell S, Hamburg A, Gover O, et al. Beta cells intrinsically sense and limit their secretory activity via mTORC1-RhoA signaling. Cell Rep. 2025;44(5):115647. doi:10.1016/j.celrep.2025.115647
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[13] Ben-Sahra I, Hoxhaj G, et al. mTORC1 induces purine synthesis through control of the mitochondrial tetrahydrofolate cycle. Science. 2016;351(6274):728-733. doi:10.1126/science.aad0489
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[16] Li Z, Wang Y, Zhang Y, et al. mTOR signaling pathway in gout: from mechanism to therapy[J]. Arthritis Res Ther, 2023, 25(1):1-12.
[17] Chen X, Zhang Y, Wang Y, et al. Autophagy in gout: mechanisms and therapeutic implications[J]. Cell Death Dis, 2022, 13(8):715.
[18] Dai Q, Xu Z, Ma X, et al. mTOR/Raptor signaling is critical for skeletogenesis in mice through the regulation of Runx2 expression. Cell Death Differ. 2017;24(11):1886-1899. doi:10.1038/cdd.2017.110
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[20] Shi M, Sun P, Chai F. Epimedium Brevicornu and Curculigo orchioides inhibit osteoclast autophagy by degrading the level of miRNA-199 to regulate the mTOR signaling pathway. J Orthop Surg Res. 2025;20(1):631. Published 2025 Jul 9. doi:10.1186/s13018-025-06043-0
[21] Liang C, Guo Y, Liu Y, et al. The mTOR signaling pathway mediates the phenotypic switch between adipocytes and osteocytes in mice with obesity-related osteoporosis. Eur J Med Res. 2025;30(1):741. Published 2025 Aug 13. doi:10.1186/s40001-025-02954-0
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[23] Tang H, Zhu S, Chen K, Yuan S, Hu J, Wang H. IL-17A regulates autophagy and promotes osteoclast differentiation through the ERK/mTOR/Beclin1 pathway. PLoS One. 2023;18(2):e0281845. Published 2023 Feb 16. doi:10.1371/journal.pone.0281845
[24] Wang J, Xu C, Zhang J, et al. RhoA promotes osteoclastogenesis and regulates bone remodeling through mTOR-NFATc1 signaling. Mol Med. 2023;29(1):49. Published 2023 Apr 5. doi:10.1186/s10020-023-00638-1
[25] Wang L, Wang N, Zhang W, et al. Therapeutic potential of a dual mTORC1/2 inhibitor for osteoporosis by targeting osteoclast differentiation and bone resorption[J]. Bone Research, 2022, 10: 13.
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