Semaglutide treatment in a rat model of high fat diet-induced obesity normalized increased cardiomyocyte calcium transients and sarcomere shortening.
Does in vivo treatment with semaglutide affect excitation-contraction coupling in a rat model of high fat diet-induced obesity?
Semaglutide normalizes increased cardiomyocyte calcium transients in a rat model of obesity, providing a potential mechanistic explanation for its benefits in HFpEF and adverse effects in HFrEF.
AIMS: Obesity increases the risk of heart failure with preserved (HFpEF), but not reduced ejection fraction (HFrEF). The glucagon-like peptide-1 receptor agonist (GLP-1-RA) semaglutide improves outcome of patients with obesity with or without HFpEF, while GLP-1-RAs were associated with adverse outcome in patients with HFrEF. Here, we investigate the effect of in vivo treatment with semaglutide on excitation-contraction coupling in a rat model of obesity. METHODS AND RESULTS: transients and sarcomere shortening further despite similar effects on body weight. CONCLUSIONS: load and LTCC currents. Because increased LTCC currents were previously traced to cardiac hypertrophy, these effects may explain why GLP-1-RAs provide benefits for patients with obesity with or without HFpEF, but rather adverse outcome in HFrEF.
Sequeira et al. (Thu,) conducted a other in Obesity. Semaglutide was evaluated on Cardiomyocyte calcium transients and sarcomere shortening. Semaglutide treatment in a rat model of high fat diet-induced obesity normalized increased cardiomyocyte calcium transients and sarcomere shortening.