Ecotoxicology and environmental safetyDec 6, 2025

How GLP-1 Receptor Agonists Combat Muscle Loss Caused by TBT

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗

Updated Jan 1, 2026

Abstract

Tributyltin (TBT) reduced muscle cell viability and size, but these effects were significantly mitigated by GLP-1 receptor agonists.

TBT exposure led to decreased cell viability and diameter in muscle cells, alongside increased markers of cell death and muscle wasting.
Administration of GLP-1 receptor agonists, such as exendin-4 and liraglutide, countered the negative effects of TBT on muscle cells.
In mice, TBT resulted in reduced muscle mass and grip strength, increased markers for cell death, and altered signaling pathways related to muscle atrophy.
GLP-1 receptor expression was decreased by TBT but was restored with the treatment of exendin-4.
The protective effects of GLP-1 receptor agonists suggest a potential therapeutic approach to combat TBT-induced muscle degeneration.

Simplified

Tributyltin (TBT), an endocrine disruptor, has been shown to exert pathological effects on skeletal muscle, though the underlying mechanisms remain incompletely understood. This study investigated the role of glucagon-like peptide-1 receptor (GLP-1R) in TBT-induced myopathy both in vitro and in vivo. GLP-1R agonists (GLP-1RAs), exendin-4 (Ex-4) and liraglutide (Lira), were tested in C2C12 myotubes (25-500 nM) exposed to TBT (0.25 μM) and in mice orally administered TBT (25 μg/kg/day) with Ex-4 (2.5 μg/kg/day) for 8 weeks. In myotubes, TBT reduced cell viability and diameter and increased apoptosis- and atrophy-related proteins, effects that were significantly mitigated by either Ex-4 or Lira. Both agents shifted myotube diameter distributions toward larger sizes, indicating attenuation of atrophy. TBT decreased GLP-1R protein expression, which was restored by Ex-4. In mice, reduced soleus muscle mass, cross-sectional area, and hindlimb grip strength, increased apoptotic and atrophy markers, and suppressed ERK and FoxO1 phosphorylation; these effects were reversed by Ex-4. GLP-1R expression in soleus muscle, downregulated by TBT, was restored with Ex-4. These findings demonstrate that GLP-1RAs protect against TBT-induced muscle wasting in vitro, with Ex-4 showing in vivo efficacy through restoration of GLP-1R expression and normalization of apoptosis- and atrophy-related signaling.

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Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

PubMed

How GLP-1 Receptor Agonists Combat Muscle Loss Caused by TBT

Abstract

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Abstract

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