Mitigation of chronic glucotoxicity-mediated skeletal muscle atrophy by arachidonic acid
Akash Mitra1, Shanooja Shanavas1, Debajit Chaudhury1
1Stem Cells and Regenerative Medicine Centre, Yenepoya Research Centre, Yenepoya Deemed to be University, University Road, Deralakatte, Mangalore 575018, Karnataka, India.
Abstract:
Toxicity caused by chronic hyperglycemia is a significant factor affecting skeletal muscle myogenesis, resulting in diabetic myopathy. Chronic and persistent hyperglycemia causes activation of the atrophy-related pathways in the skeletal muscles, which eventually results in inflammation and muscle degeneration. To counteract this process, various bioactive compound has been studied for their reversal or hypertrophic effect. In this study, we explored the molecular mechanisms associated with reversing glucotoxicity's effect in C2C12 cells by arachidonic acid (AA). We found a substantial increase in the pro-inflammatory cytokines and ROS production in hyperglycemic conditions, mitigated by AA supplementation. We found that AA supplementation restored protein synthesis that was downregulated under glucotoxicity conditions. AA enhanced myogenesis by suppressing high glucose induced inflammation and ROS production and enhancing protein synthesis. These results imply that AA has cytoprotective actions against hyperglycemia-induced cytotoxicity.
Insights
Arachidonic acid (AA) combats diabetic myopathy by mitigating hyperglycemia-induced inflammation and oxidative stress in muscle cells. AA supplementation restores protein synthesis, promoting myogenesis and offering cytoprotective effects against high glucose toxicity.
Area of Science:
- Biochemistry
- Molecular Biology
- Cell Biology
Background:
- Chronic hyperglycemia, a hallmark of diabetes, impairs skeletal muscle regeneration (myogenesis) and leads to diabetic myopathy.
- Hyperglycemia activates muscle atrophy pathways, causing inflammation and degeneration.
Purpose of the Study:
- To investigate the molecular mechanisms by which arachidonic acid (AA) reverses glucotoxicity in C2C12 muscle cells.
- To assess AA's potential to counteract hyperglycemia-induced inflammation, oxidative stress, and impaired protein synthesis.
Main Methods:
- C2C12 myoblasts were exposed to high glucose conditions to induce glucotoxicity.
- Arachidonic acid (AA) supplementation was administered to assess its protective effects.
- Pro-inflammatory cytokines, reactive oxygen species (ROS) production, and protein synthesis levels were measured.
Main Results:
- High glucose significantly increased pro-inflammatory cytokines and ROS production, while decreasing protein synthesis.
- AA supplementation effectively mitigated the increase in inflammation and ROS.
- AA restored downregulated protein synthesis, indicating enhanced myogenesis.
Conclusions:
- Arachidonic acid (AA) demonstrates cytoprotective properties against hyperglycemia-induced cytotoxicity in skeletal muscle cells.
- AA suppresses high glucose-induced inflammation and oxidative stress, while promoting protein synthesis and myogenesis.
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