Article Impact Level: HIGH Data Quality: STRONG Summary of JACC: Basic to Translational Science. https://doi.org/10.1016/j.jacbts.2024.07.006 Dr. Matthew D. Martens et al.
Points
- Semaglutide, a GLP-1 receptor agonist, induced significant weight loss (30% of body weight) and fat mass reduction (65%) in obese mice, alongside reductions in cardiac and skeletal muscle mass.
- Semaglutide treatment reduced left ventricular (LV) mass and cardiomyocyte size in obese and lean mice without impairing systolic or diastolic function.
- Semaglutide caused an 8.2% reduction in skeletal muscle mass in lean mice, consistent with lean mass loss observed in prior studies of obese mice.
- The reduction in cardiac size was not linked to fibrosis or muscle atrophy-related gene expression, suggesting semaglutide alters cardiac structure via mechanisms independent of atrophy pathways.
- The study raises concerns about the potential impact of GLP-1RAs on cardiac structure, emphasizing the need for careful monitoring in clinical trials, particularly for patients with cardiovascular conditions or heart failure risks.
Summary
This study investigates the effects of semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), on mice’s cardiac and skeletal muscle mass. The research explored how semaglutide-induced weight loss, a common therapeutic effect, influences cardiac mass and skeletal muscle and its implications for heart failure and cardiovascular disease (CVD). Male mice were first fed a high-fat, high-sucrose diet (HFHS) to induce obesity, gaining an average body weight (BW) of 18.6 ± 1.2 g. After switching to a regular chow diet, semaglutide-treated mice lost approximately 30% of their BW and 65% of fat mass compared to vehicle-treated mice. Despite no significant changes in systolic or diastolic function, semaglutide-treated mice exhibited a marked reduction in left ventricular (LV) mass and cardiomyocyte size.
The study revealed that semaglutide treatment in both obese and lean mice resulted in a reduction of cardiac mass and cardiomyocyte area, indicating a decrease in heart muscle size. Specifically, semaglutide caused an 8.2% reduction in skeletal muscle mass over 3 weeks in lean mice, consistent with the observed loss of lean body mass in previous studies using obese mice. However, the reduction in LV mass was not associated with changes in gene expression related to fibrosis or muscle atrophy, such as Murf1 and Atrogin-1, suggesting that the loss in cardiac size may not be due to atrophy. This indicates that semaglutide may induce changes in cardiac structure independent of recognized pathways for atrophy.
The findings highlight the potential long-term impact of GLP-1RAs on cardiac structure, particularly in individuals with existing cardiovascular conditions. While GLP-1RAs like semaglutide have shown benefits for weight loss, their effect on cardiac mass in the absence of prohypertrophic stressors raises concerns for individuals at risk of heart failure. The study calls for careful cardiac structure and function evaluation in clinical trials involving GLP-1RA therapies, especially in patients with cardiovascular comorbidities.
Link to the article: https://www.sciencedirect.com/science/article/pii/S2452302X24002869
References Martens, M. D., Abuetabh, Y., Schmidt, M. A., Zolondek, M. C. P., Silver, H. L., Levasseur, J. L., Ferdaoussi, M., & Dyck, J. R. B. (2024). Semaglutide reduces cardiomyocyte size and cardiac mass in lean and obese mice. JACC: Basic to Translational Science. https://doi.org/10.1016/j.jacbts.2024.07.006
