Melatonin Ameliorates Organellar Calcium Homeostasis, Improving Endoplasmic Reticulum Stress-Mediated Apoptosis in the Vastus Lateralis Muscle of Both Sexes of Obese Diabetic Rats
Metadatos
Mostrar el registro completo del ítemAutor
Salagre Simón, Diego; Navarro-Alarcón, Miguel; Gerardo González, Luis; A. Elrayess, Mohamed; Villalón-Mir, Marina; Haro López, Rocío; Agil, AhmadEditorial
MDPI
Materia
melatonin obesity type 2 diabetes
Fecha
2024-12-26Referencia bibliográfica
Salagre Simón, D. et. al. Antioxidants 2025, 14, 16 [https://doi.org/10.3390/antiox14010016]
Patrocinador
Grant PID2021-125900OB-I00 funded by MCIN/AEI/10.13039/ 501100011033; ERDF “A way of making Europe”Resumen
Endoplasmic reticulum (ER) stress is a crucial factor in the progression of obesityrelated
type 2 diabetes (diabesity), contributing to skeletal muscle (SKM) dysfunction,
calcium imbalance, metabolic inflexibility, and muscle atrophy. The ER and mitochondria
together regulate intracellular calcium levels, and melatonin, a natural compound with
antioxidant properties, may alleviate these challenges. Our previous research showed
that melatonin raises intracellular calcium and preserves muscle structure by enhancing
mitochondrial function in obese diabetic rats. This study further explores melatonin’s
potential to reduce ER stress in the vastus lateralis (VL) muscle by modulating the unfolded
protein response (UPR) and restoring calcium levels disrupted by diabesity. Five-week-old
Zücker diabetic fatty (ZDF) rats and lean littermates of both sexes were divided into control
and melatonin-treated groups (10 mg/kg/day for 12 weeks). Flame atomic absorption
spectrometry results showed that melatonin restored VL intraorganellar calcium homeostasis,
increasing calcium levels in mitochondria and reducing them in the ER by raising
the activity and expression of calcium transporters in both sexes of ZDF rats. Melatonin
also decreased ER stress markers (GRP78, ATF6, IRE1α, and PERK) and reduced proapoptosis
markers (Bax, Bak, P-JNK, cleaved caspase 3 and 9) while increasing Bcl2 levels
and melatonin receptor 2 (MT2) expression. These findings suggest that melatonin may
protect against muscle atrophy in obese and diabetic conditions by mitigating ER stress
and calcium imbalance, highlighting its therapeutic potential.