Semaglutide-induced weight loss improves mitochondrial energy efficiency in skeletal muscle

Nov 28, 2024bioRxiv : the preprint server for biology

Weight loss from semaglutide improves energy use in muscle cells

AI simplified

GLP-1 Therapies on OpenScience ↗PubMed ↗DOI ↗OA ↗

Abstract

Semaglutide treatment significantly improved skeletal muscle oxidative phosphorylation efficiency.

Weight loss from semaglutide led to reductions in both fat and lean mass.
Skeletal muscle efficiency was assessed by measuring ATP production per oxygen consumed.
Changes in mitochondrial proteins related to complex III assembly were observed.
No substantial changes were noted in the overall abundance of oxidative phosphorylation subunits.
Future studies may explore the relationship between improved mitochondrial efficiency and weight regain.

AI simplified

OBJECTIVE: Glucagon-like peptide 1 receptor agonists (e.g. semaglutide) potently induce weight loss and thereby reducing obesity-related complications. However, weight regain occurs when treatment is discontinued. An increase in skeletal muscle oxidative phosphorylation (OXPHOS) 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 rate of ATP production and Oconsumption were measured by a high-resolution respirometry and fluorometry to determine OXPHOS efficiency in skeletal muscle at these 2 timepoints. 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 (P/O) in permeabilized muscle fibers. Mitochondrial proteomic analysis revealed changes restricted to two proteins linked to complex III assembly (Lyrm7 and Ttc1, 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.

Full Text

Full text is available at the source.

View full text ↗

Semaglutide-induced weight loss improves mitochondrial energy efficiency in skeletal muscle

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the glp-1 therapies brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the glp-1 therapies brief