20.500.12556/RUP-22859 Targeting skeletal muscle melatonin-MT2 signaling to attenuate the obesity-cancer axis a metabolic perspective 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. 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 true false true Angleški jezik Angleški jezik Članek v reviji 2026-03-26 23:00:09 2026-03-26 23:00:09 2026-03-27 03:05:06 0000-00-00 00:00:00 2026 0 0 str. 1-50 2026 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 2026-03-25 577.1:616-006 0327-9545 10.32604/biocell.2026.079591 273262851 https://doi.org/10.32604/biocell.2026.079591 1 23e5542b-295f-11f1-9e8d-005056ac49c0 https://repozitorij.upr.si/Dokument.php?lang=slv&id=33367 https://www.techscience.com/biocell/online/detail/26315 1 220339fd-295f-11f1-9e8d-005056ac49c0 https://repozitorij.upr.si/Dokument.php?lang=slv&id=33366 RAZ_Jurdana_Mihaela_2026.pdf RAZ_Jurdana_Mihaela_2026.pdf 1 609669CC4E58EF966ED2C7ED1FCC4D2E e477b641baf979bae3307a903df1d79f3bc8584c3f3557a92fd768198f30ba7c 67e98323-295f-11f1-9e8d-005056ac49c0 https://repozitorij.upr.si/Dokument.php?lang=slv&id=33368 Fakulteta za vede o zdravju 0 0 0