Melatonin Improves Skeletal Muscle Structure and Oxidative Phenotype by Regulating Mitochondrial Dynamics and Autophagy in Zücker Diabetic Fatty Rat
Metadatos
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Salagre Simón, Diego; Raya Álvarez, Enrique Germán; Cendán Martínez, Cruz Miguel; Aouichat, Samira; Agil Abdalla, Mhmad AhmadEditorial
MDPI
Materia
Melatonin Mitochondrial fission-fusion; autophagy Oxidative stress Skeletal muscle Red vastus lateralis Muscle fiber composition Diabesity ZDF rat
Fecha
2023-07-27Referencia bibliográfica
Salagre, D.; Raya Álvarez, E.; Cendan, C.M.; Aouichat, S.; Agil, A. Melatonin Improves Skeletal Muscle Structure and Oxidative Phenotype by Regulating Mitochondrial Dynamics and Autophagy in Zücker Diabetic Fatty Rat. Antioxidants 2023, 12, 1499. [https://doi.org/10.3390/antiox12081499]
Patrocinador
PID2021-125900OB-I00 from the Ministerio de Ciencia e Innovación (Spain); European Regional Development Fund (ERDF); B-CTS102-UGR from European Regional Development Fund (ERDF)Resumen
Obesity-induced skeletal muscle (SKM) inflexibility is closely linked to mitochondrial
dysfunction. The present study aimed to evaluate the effects of melatonin on the red vastus lateralis
(RVL) muscle in obese rat models at the molecular and morphological levels. Five-week-old male
Zücker diabetic fatty (ZDF) rats and their age-matched lean littermates (ZL) were orally treated
either with melatonin (10 mg/kg body weight (BW)/24 h) (M–ZDF and M–ZL) or non-treated
(control) (C–ZDF and C–ZL) for 12 weeks. Western blot analysis showed that mitochondrial fission,
fusion, and autophagy were altered in the C-ZDF group, accompanied by reduced SIRT1 levels.
Furthermore, C-ZDF rats exhibited depleted ATP production and nitro-oxidative stress, as indicated
by increased nitrites levels and reduced SOD activity. Western blotting of MyH isoforms demonstrated
a significant decrease in both slow and fast oxidative fiber-specific markers expression in the C-ZDF
group, concomitant with an increase in the fast glycolytic fiber markers. At the tissue level, marked
fiber atrophy, less oxidative fibers, and excessive lipid deposition were noted in the C-ZDF group.
Interestingly, melatonin treatment partially restored mitochondrial fission/fusion imbalance in the
RVL muscle by enhancing the expression of fission (Fis1 and DRP1) markers and decreasing that of
fusion (OPA1 and Mfn2) markers. It was also found to restore autophagy, as indicated by increased
p62 protein level and LC3BII/I ratio. In addition, melatonin treatment increased SIRT1 protein
level, mitochondrial ATP production, and SOD activity and decreased nitrites production. These
effects were associated with enhanced oxidative phenotype, as evidenced by amplified oxidative
fiber-specific markers expression, histochemical reaction for NADH enzyme, and muscular lipid
content. In this study, we showed that melatonin might have potential therapeutic implications for
obesity-induced SKM metabolic inflexibility among patients with obesity and T2DM