Glucagon-like peptide-1 receptor (GLP-1R) agonists prevent tributyltin-induced muscle atrophy/wasting via restoring GLP-1R signaling in vitro and in mice.
Level 5 - mechanism / opinion, no new human data
Preclinical in vitro and animal experimental study without human subjects.
PubMed 41352264 · doi:10.1016/j.ecoenv.2025.119523
What was done
Researchers evaluated the protective effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) against tributyltin (TBT)-induced muscle wasting. In vitro, C2C12 myotubes were treated with TBT (0.25 μM) alone or with exendin-4 (Ex-4, 25–500 nM) or liraglutide. In vivo, mice were administered oral TBT (25 μg/kg/day) with or without Ex-4 (2.5 μg/kg/day) for 8 weeks. Outcomes assessed included cell viability, myotube diameter, soleus muscle mass, cross-sectional area, hindlimb grip strength, GLP-1R protein expression, ERK and FoxO1 phosphorylation, and markers of apoptosis and muscle atrophy.
What was found
In myotubes, TBT reduced cell viability, decreased diameter, downregulated GLP-1R expression, and elevated apoptotic and atrophic proteins; both Ex-4 and liraglutide mitigated these changes and shifted diameter distributions toward larger sizes (exact quantitative values not reported in abstract). In mice, TBT decreased soleus muscle mass, cross-sectional area, grip strength, GLP-1R expression, and phosphorylation of ERK and FoxO1 while increasing apoptotic and atrophy markers. Ex-4 co-treatment reversed all observed TBT-induced muscular and signaling deficits (exact numerical values not reported).
Why it matters
This study identifies GLP-1 receptor signaling as a mechanistic pathway in toxin-induced muscle atrophy and suggests that GLP-1R agonists can preserve skeletal muscle mass and strength in preclinical models.
Limits
The study is restricted entirely to cell culture and mouse models, so applicability to human toxicology and muscle pathology remains unproven. The abstract does not report sample sizes, baseline animal characteristics, or numerical effect sizes and confidence intervals. Furthermore, findings from chemical-induced toxicity (TBT) may not generalize to other etiologies of sarcopenia or muscle wasting.
Cited by
- supports GLP-1 receptors are expressed on skeletal muscle cells and bone cells.