Glucagon-like peptide 1 receptor agonists (GLP-1RAs) are widely prescribed to treat obesity and related diseases such as diabetes, cardiovascular disease, and sleep apnea. The remarkable success of GLP-1RAs in treating these diseases has been tempered by the dramatic loss of muscle mass and function associated with the treatment. Our lab has previously demonstrated the capacity of microbial-derived exerkines (MDEs) pipecolic acid and succinate (PAS) to ameliorate losses of skeletal muscle size and function during disuse atrophy. In the current study, we treated diet-induced obesity (DIO) mice with vehicle (VEH), semaglutide (SEM), or semaglutide and PAS (SEM+PAS) for one week during high fat diet and assessed body composition and skeletal muscle phenotype and function. Treatment with PAS protects against SEM-induced losses in lean mass and rescues skeletal muscle cross-sectional area and function. These findings demonstrate the therapeutic potential of MDEs in protecting against GLP-1RA-induced losses in skeletal muscle size and function. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
Burke et al. (Fri,) studied this question.