Targeting skeletal muscle melatonin-MT2 signaling to attenuate the obesity-cancer axis : a metabolic perspective

Jurdana, Mihaela (avtor), Žiberna, Lovro (avtor)

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.

• Jezik: Angleški jezik
• Ključne besede: 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
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.02 - Pregledni znanstveni članek
• Organizacija: MF - Medicinska fakulteta ; FFA - Fakulteta za farmacijo
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2026
• Št. strani: 50 str.
• Številčenje: 50, iss. 8
• PID: 20.500.12556/RUL-186237
• UDK: 577.1:616-006
• ISSN pri članku: 0327-9545
• DOI: 10.32604/biocell.2026.079591
• COBISS.SI-ID: 273262851
• Datum objave v RUL: 28.08.2026

Gradivo je del revije

• Naslov: Biocell
• Skrajšan naslov: Biocell
• Založnik: Tech Science Press
• ISSN: 0327-9545
• COBISS.SI-ID: 19518247

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.

Projekti

• Financer: ARIS - Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije
• Številka projekta: P3-0067
• Naslov: Farmakologija in farmakogenomika

• Financer: ARIS - Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije
• Številka projekta: P3-0003
• Naslov: Razvoj in ovrednotenje novih terapij za zdravljenje malignih tumorjev