title: Melatonin protects against uric acid-induced mitochondrial dysfunction, oxidative stress, and triglyceride accumulation in C2C12myotubes.
abstract: Excess uric acid has been shown to induce oxidative stress, triglyceride accumulation, and mitochondrial dysfunction in the liver and is an independent predictor of type-2 diabetes. Skeletal muscle plays a dominant role in type 2 diabetes and presents a large surface area to plasma uric acid. However, the effects of uric acid on skeletal muscle are underinvestigated. Our aim was therefore to characterize the effects of excessive uric acid on oxidative stress, triglyceride content, and mitochondrial function in skeletal muscle C2C12myotubes and assess how these are modulated by the antioxidant molecule melatonin. Differentiated C2C12myotubes were exposed to 750 µM uric acid or uric acid + 10 nM melatonin for 72 h. Compared with control, uric acid increased triglyceride content by ~237%, oxidative stress by 32%, and antioxidant capacity by 135%. Uric acid also reduced endogenous ROUTINE respiration, complex II-linked oxidative phosphorylation, and electron transfer system capacities. Melatonin counteracted the effects of uric acid without further altering antioxidant capacity. Our data demonstrate that excess uric acid has adverse effects on skeletal muscle similar to those previously reported in hepatocytes and suggest that melatonin at a low physiological concentration of 10 nM may be a possible therapy against some adverse effects of excess uric acid.NEW & NOTEWORTHYFew studies have investigated the effects of uric acid on skeletal muscle. This study shows that hyperuricemia induces mitochondrial dysfunction and triglyceride accumulation in skeletal muscle. The findings may explain why hyperuricemia is an independent predictor of diabetes.
authors.affiliation: Division of Exercise Science and Sports Medicine (ESSM), Department of Human Biology, University of Cape Town, Newlands, South Africa; and.
authors.forename: Gerald J
authors.initials: GJ
authors.lastname: Maarman
authors.affiliation: Division of Exercise Science and Sports Medicine (ESSM), Department of Human Biology, University of Cape Town, Newlands, South Africa; and.
authors.forename: Brittany M
authors.initials: BM
authors.lastname: Andrew
authors.affiliation: Division of Chemical Pathology, Department of Pathology, University of Cape Town, Cape Town, South Africa.
authors.forename: Dee M
authors.initials: DM
authors.lastname: Blackhurst
authors.affiliation: Division of Exercise Science and Sports Medicine (ESSM), Department of Human Biology, University of Cape Town, Newlands, South Africa; and 01374266ed@gmail.com.
authors.forename: Edward O
authors.initials: EO
authors.lastname: Ojuka
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002460:Cell Line; D019069:Cell Respiration / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000503:physiopathology; D004579:Electron Transport / Q000502:physiology; D008550:Melatonin / Q000378:metabolism*; D051379:Mice; D008928:Mitochondria / Q000378:metabolism* / Q000502:physiology; D028361:Mitochondrial Diseases / Q000378:metabolism* / Q000503:physiopathology; D018485:Muscle Fibers, Skeletal / Q000378:metabolism* / Q000502:physiology; D018482:Muscle, Skeletal / Q000378:metabolism / Q000503:physiopathology; D018384:Oxidative Stress / Q000502:physiology*; D014280:Triglycerides / Q000378:metabolism*; D014527:Uric Acid / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D014280:Triglycerides; D014527:Uric Acid; D008550:Melatonin
keywords: melatonin; mitochondrial dysfunction; oxidative stress; uric acid