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Effects of uric acid and melatonin exposure on mitochondrial complex‐I respiration, triglyceride accumulation and aconitase activity in skeletal muscle cells
Author(s) -
Maarman Gerald Jerome,
Andrew Brittany Morgan,
Blackhurst Dee,
Ojuka Edward
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1100.14
Subject(s) - endocrinology , medicine , hyperuricemia , triglyceride , lipogenesis , uric acid , chemistry , oxidative stress , skeletal muscle , myogenesis , mitochondrion , biology , biochemistry , lipid metabolism , cholesterol
Background Hyperuricemia is associated with gout, hepatic steatosis and type 2 diabetes. It induces oxidative stress, lipogenesis and mitochondrial dysfunction in the liver. However, the skeletal muscle is the greatest surface area exposed to hyperuricemia and yet no studies have investigated its effects on skeletal muscle. Aims To establish whether hyperuricemia modulates mitochondrial function, oxidative stress and triglyceride accumulation in myotubes and whether antioxidant treatment with melatonin can counteract these effects. Methods Differentiated C2C12 myotubes were exposed to uric acid (750μM, 72 hrs.) or uric acid + melatonin (10nM melatonin, 72 hrs). Mitochondrial function was assessed (high‐resolution respirometry), spectrophotometry was used to assess oxidative damage to aconitase and triglyceride content. All values were compared to respective control groups (without uric acid and without melatonin). Results Uric acid (1) reduced OXPHOS (60%) in the presence of pyruvate, glutamate and malate, (2) reduced aconitase activity by 37% and (3) increased triglyceride accumulation (52%) in C2C12 myotubes. Melatonin treatment restored OXPHOS (40%) and reduced triglyceride content (47%). Conclusion Hyperuricemia dysregulates complex‐1 mediated mitochondrial respiration, induces damage to aconitase and triglyceride accumulation. Melatonin restored complex‐1 mediated mitochondrial function and normalized triglyceride accumulation. Melatonin could therefore be considered a therapy against hyperuricemia. Support or Funding Information National Research Foundation (South Africa) and the University of Cape Town.