Mitochondrial Adaptations in Skeletal Muscle Following Incretin-Based Therapies: In Vitro - PubMed
5 hours ago
- #skeletal muscle
- #GLP-1RA
- #mitochondrial health
- Incretin-based therapies like GLP-1RAs, dual GLP-1/GIP agonists, and amylin analogues show weight loss benefits but their effects on skeletal muscle mitochondrial function under metabolic stress are unclear.
- Study investigated semaglutide (GLP-1RA), tirzepatide (dual GLP-1/GIP agonist), and cagrilintide (amylin analogue) on mitochondrial function in C2C12 myotubes under healthy and lipotoxic conditions.
- Palmitic acid (PA) impaired mitochondrial function, reducing basal oxygen consumption rate (OCR) by 22% and ATP production by 25%.
- Semaglutide and cagrilintide transiently reduced basal respiration and ATP production in healthy myotubes at 48h, resolving by 5 days.
- Tirzepatide increased maximal respiration and spare respiratory capacity after 5 days in healthy myotubes.
- In PA-treated myotubes, semaglutide and cagrilintide initially worsened mitochondrial impairment but effects resolved by Day 5.
- Tirzepatide initially suppressed mitochondrial function in PA-treated myotubes but reversed effects by Day 5, improving ATP production, basal respiration, and coupling efficiency.
- mtDNA content remained unchanged across all conditions.
- Similar responses were noted in human myotubes, with tirzepatide significantly improving maximal respiration at 5 days.
- Tirzepatide promoted sustained improvements in mitochondrial respiration under both healthy and lipotoxic conditions, suggesting potential benefits for skeletal muscle health in metabolic disease.