Chronic melatonin treatment improves obesity by inducing uncoupling of skeletal muscle SERCA-SLN mediated by CaMKII/AMPK/PGC1α pathway and mitochondrial biogenesis in female and male Zücker diabetic fatty rats

Salagre, D.; Navarro-Alarcón, M.; Villalón-Mir, M.; Alcázar-Navarrete, B.; Gómez-Moreno, G.; Tamimi, F.; Agil, A.

doi:10.1016/j.biopha.2024.116314

Biomedicine & Pharmacotherapy

2024

DOI: 10.1016/j.biopha.2024.116314

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Chronic melatonin treatment improves obesity by inducing uncoupling of skeletal muscle SERCA-SLN mediated by CaMKII/AMPK/PGC1α pathway and mitochondrial biogenesis in female and male Zücker diabetic fatty rats

D. Salagre,

M. Navarro-Alarcón,

M. Villalón-Mir

et al.

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Cited by 4 publications

References 116 publications

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Melatonin induces fiber switching by improvement of mitochondrial oxidative capacity and function via NRF2/RCAN/MEF2 in the vastus lateralis muscle from both sex Zücker diabetic fatty rats

Salagre,

Bajit,

Fernández-Vázquez

et al. 2025

Free Radical Biology and Medicine

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Melatonin induces fiber switching by improvement of mitochondrial oxidative capacity and function via NRF2/RCAN/MEF2 in the vastus lateralis muscle from both sex Zücker diabetic fatty rats

Salagre,

Bajit,

Fernández-Vázquez

et al. 2025

Free Radical Biology and Medicine

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Pleiotropic Regulation of PGC-1α in Tumor Initiation and Progression

Zhang,

Zhao,

2024

Antioxidants & Redox Signaling

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Melatonin Ameliorates Organellar Calcium Homeostasis, Improving Endoplasmic Reticulum Stress-Mediated Apoptosis in the Vastus Lateralis Muscle of Both Sexes of Obese Diabetic Rats

Salagre,

Navarro-Alarcón,

González

et al. 2024

Antioxidants

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Endoplasmic reticulum (ER) stress is a crucial factor in the progression of obesity-related 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 pro-apoptosis 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.

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Chronic melatonin treatment improves obesity by inducing uncoupling of skeletal muscle SERCA-SLN mediated by CaMKII/AMPK/PGC1α pathway and mitochondrial biogenesis in female and male Zücker diabetic fatty rats

Cited by 4 publications

References 116 publications

Melatonin induces fiber switching by improvement of mitochondrial oxidative capacity and function via NRF2/RCAN/MEF2 in the vastus lateralis muscle from both sex Zücker diabetic fatty rats

Melatonin induces fiber switching by improvement of mitochondrial oxidative capacity and function via NRF2/RCAN/MEF2 in the vastus lateralis muscle from both sex Zücker diabetic fatty rats

Pleiotropic Regulation of PGC-1α in Tumor Initiation and Progression

Melatonin Ameliorates Organellar Calcium Homeostasis, Improving Endoplasmic Reticulum Stress-Mediated Apoptosis in the Vastus Lateralis Muscle of Both Sexes of Obese Diabetic Rats

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