| Title: | Targeting skeletal muscle melatonin-MT2 signaling to attenuate the obesity-cancer axis : a metabolic perspective |
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| Authors: | ID Jurdana, Mihaela (Author)
ID Žiberna, Lovro (Author) |
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| Files: |  https://doi.org/10.32604/biocell.2026.079591
https://www.techscience.com/biocell/online/detail/26315
 RAZ_Jurdana_Mihaela_2026.pdf (1,56 MB)
MD5: 609669CC4E58EF966ED2C7ED1FCC4D2E
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| Language: | English |
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| Work type: | Article |
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| Typology: | 1.02 - Review Article |
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| Organization: | FVZ - Faculty of Health Sciences
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| Abstract: | Obesity and metabolic syndrome promote malignancies through chronic inflammation and sustained activation of insulin and insulin-like growth factor-1 (IGF-1) signaling. Skeletal muscle is central to this tumor-promoting milieu because it governs insulin-stimulated glucose disposal, lipid oxidation, and endocrine crosstalk. This narrative review explores whether melatonin signaling in skeletal muscle, particularly via melatonin receptor 2 (MT2), represents a modifiable node within the obesity–cancer axis. Experimental evidence indicates that melatonin activates MT2-linked Gi/o and calcium-sensitive pathways converging on phosphoinositide 3-kinase–protein kinase B (PI3K–Akt), extracellular signal-regulated kinases (ERK), and calcium/calmodulin-dependent protein kinase II–adenosine monophosphate-activated protein kinase–peroxisome proliferator-activated receptor gamma coactivator 1-alpha (CaMKII–AMPK–PGC-1α) signaling. These pathways enhance insulin sensitivity, mitochondrial function, and lipid partitioning while reducing myosteatosis and cellular stress. By improving muscle quality, melatonin may lower systemic insulin and IGF-1 drive and inflammatory adipokine tone that fuel tumor-promoting PI3K–Akt–mammalian target of rapamycin (mTOR) signaling. However, human evidence remains limited and timing-dependent. Melatonin exposure in the fed state or near carbohydrate intake may worsen glycemia, particularly in carriers of melatonin receptor 1B (MTNR1B) risk alleles. Chronobiology-informed, genotype-guided trials with detailed muscle phenotyping and cancer-relevant endpoints are warranted. |
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| Keywords: | melatonin, melatonin receptor 1, melatonin receptor 2, melatonin receptor 1A gene, melatonin receptor 1B gene, skeletal muscle, insulin resistance, myosteatosis, sarcopenic obesity, myokines, obesity-related cancer |
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| Publication status: | Published |
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| Publication version: | Version of Record |
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| Publication date: | 25.03.2026 |
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| Year of publishing: | 2026 |
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| Number of pages: | str. 1-50 |
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| PID: | 20.500.12556/RUP-22859  |
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| UDC: | 577.1:616-006 |
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| ISSN on article: | 0327-9545 |
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| DOI: | 10.32604/biocell.2026.079591 |
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| COBISS.SI-ID: | 273262851 |
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| Publication date in RUP: | 26.03.2026 |
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| Views: | 77 |
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| Downloads: | 9 |
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