Melatonin Improves Levels of Zn and Cu in the Muscle of Diabetic Obese Rats Navarro Alarcón, Miguel Gil Hernández, Fernando Sánchez González, Cristina Llopis González, Juan Villalón Mir, Marina Olmedo Palma, Pablo Alarcón Guijo, Pablo Salagre Simón, Diego Gaona, Lorena Paredes, Mario Agil Abdalla, Mhmad Ahmad Melatonin Zinc Copper Diabetic obese rat Melatonin improves metabolic alterations associated with obesity and its diabetes (diabesity). We intend to determine whether this improvement is exerted by changing Zn and/or Cu tissue levels in liver, muscle, pancreas, and brain, and in internal (perirenal, perigonadal, and omentum) and subcutaneous lumbar white adipose tissues (IWAT and SWAT, respectively). Male Zücker diabetic fatty (ZDF) rats and lean littermates (ZL) were orally supplemented either with melatonin (10 mg/kg body weight/day) or vehicle for 6 weeks. Zn and Cu concentrations were not significantly influenced by diabesity in the analyzed tissues (p > 0.05), with the exception of Zn in liver. In skeletal muscle Zn and Cu, and in perirenal WAT, only Zn levels increased significantly with melatonin supplementation in ZDF rats (p < 0.05). This cytoplasmic Zn enhancement would be probably associated with the upregulation of several Zn influx membrane transporters (Zips) and could explain the amelioration in the glycaemia and insulinaemia by upregulating the Akt and downregulating the inhibitor PTP1B, in obese and diabetic conditions. Enhanced Zn and Cu levels in muscle cells could be related to the reported antioxidant melatonin activity exerted by increasing the Zn, Cu-SOD, and extracellular Cu-SOD activity. In conclusion, melatonin, by increasing the muscle levels of Zn and Cu, joined with our previously reported findings improves glycaemia, insulinaemia, and oxidative stress in this diabesity animal model. 2021-11-08T07:43:29Z 2021-11-08T07:43:29Z 2021 info:eu-repo/semantics/article Navarro-Alarcón, M.; Gil-Hernández, F.; Sánchez-González, C.; Llopis, J.; Villalón-Mir, M.; Olmedo, P.; Alarcón-Guijo, P.; Salagre, D.; Gaona, L.; Paredes, M.; et al. Melatonin Improves Levels of Zn and Cu in the Muscle of Diabetic Obese Rats. Pharmaceutics 2021, 13, 1535. https://doi.org/10.3390/ pharmaceutics13101535 http://hdl.handle.net/10481/71338 10.3390/pharmaceutics13101535 eng http://creativecommons.org/licenses/by/3.0/es/ info:eu-repo/semantics/openAccess Atribución 3.0 España MDPI