Semaglutide treatment improved skeletal muscle oxidative phosphorylation efficiency, measured as ATP produced per oxygen consumed.
Significant reductions in both fat and lean mass were observed with semaglutide treatment.
Mitochondrial efficiency in muscle increased, indicating enhanced energy production capabilities.
Changes in mitochondrial proteins related to complex III assembly were noted, although there were no substantial changes in overall subunit levels.
The findings suggest a potential mechanism for weight regain after discontinuation of semaglutide treatment.
Simplified
OBJECTIVE: Glucagon-like peptide-1 receptor agonists (e.g., semaglutide) potently induce weight loss, thereby reducing obesity-related complications. However, weight regain occurs when treatment is discontinued. An increase in skeletal muscle oxidative phosphorylation () efficiency upon diet-mediated weight loss has been described, which may contribute to reduced systemic energy expenditure and weight regain. We set out to determine the unknown effect of semaglutide on muscle OXPHOS efficiency.
METHODS: C57BL/6J mice were fed a high-fat diet for 12 weeks before receiving semaglutide or vehicle for 1 or 3 weeks. The rates of ATP production and oxygen (O) consumption were measured via high-resolution respirometry and fluorometry to determine OXPHOS efficiency in muscle at these two time points. 2
RESULTS: Semaglutide treatment led to significant reductions in fat and lean mass. Semaglutide improved skeletal muscle OXPHOS efficiency, measured as ATP produced per Oconsumed in permeabilized muscle fibers. Mitochondrial proteomic analysis revealed changes restricted to two proteins linked to complex III assembly (LYRM7 and TTC19; p < 0.05 without multiple corrections) without substantial changes in the abundance of OXPHOS subunits. 2
CONCLUSIONS: These data indicate that weight loss with semaglutide treatment increases skeletal muscle mitochondrial efficiency. Future studies could test whether it contributes to weight regain.
Key numbers
23%
Weight Loss After 3 Weeks
Percentage reduction in body weight after treatment.
42%
Fat Mass Reduction After 3 Weeks
Percentage decrease in fat mass following treatment with .
10%
Lean Mass Reduction After 3 Weeks
Approximate percentage decrease in lean mass after 3 weeks of treatment.
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