Semaglutide Reverses Ectopic Lipid Accumulation, Impaired Myocardial Perfusion Reserve, and Diastolic Dysfunction in...

Semaglutide (SEMA) improves cardiometabolic outcomes in obesity, but its mechanisms remain incompletely understood. We examined the effects of SEMA in mice fed a high-fat, high-sucrose diet. Obese mice were treated with SEMA and compared with pair-fed controls to account for reduced dietary intake with SEMA. Multiparametric cardiovascular magnetic resonance was used to assess epicardial adipose tissue volume and composition, myocardial fat fraction, adenosine myocardial perfusion reserve, systolic strain, and diastolic function, with histological evaluation of myocardial fibrosis. SEMA treatment reduced proinflammatory epicardial adipose tissue, reduced ectopic lipid accumulation, improved myocardial perfusion reserve, and reversed impairments in systolic and diastolic strain, whereas pair-feeding did not. Myocardial fibrosis was also reduced with SEMA treatment. These results indicate that SEMA reverses key CMR and histological features of obesity-induced cardiometabolic heart disease in mice, independent of changes in dietary intake.