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May 7, 2026JACC Basic to Translational ScienceOpen Access

Semaglutide Reverses Ectopic Lipid Accumulation, Impaired Myocardial Perfusion Reserve, and Diastolic Dysfunction in a Mouse Model of Cardiometabolic Heart Disease

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Key result

Semaglutide reverses ectopic lipid accumulation, impaired perfusion reserve, and diastolic dysfunction in cardiometabolic mouse models.

Why the study?

Semaglutide improves cardiometabolic outcomes in obesity, but its underlying mechanisms remain incompletely understood.

Does semaglutide improve myocardial perfusion, strain, and ectopic lipid accumulation in a mouse model of cardiometabolic heart disease?

Population

Mice fed a high-fat, high-sucrose diet

Comparison

Semaglutide vs pair-fed controls

Design

Preclinical animal study

Authors

TSThomas P. SkacelUniversity of VirginiaNSNemati R. SalehUniversity of VirginiaCPCaitlin M. PavelecUniversity of Virginia

Discussion

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Implication

Semaglutide improves myocardial parameters independent of weight loss in obese mice; leaves open translation to human cardiometabolic heart disease.

Key Points

  • The aim is to investigate the effects of semaglutide on cardiometabolic heart disease in a mouse model.
  • Mice were fed a high-fat, high-sucrose diet and treated with semaglutide.
  • Cardiovascular health was assessed using multiparametric magnetic resonance imaging.
  • Histological evaluation of myocardial fibrosis was performed.
  • SEMA treatment significantly reduced ectopic lipid accumulation and improved myocardial perfusion reserve (p<0.05).
  • Systolic strain and diastolic function were significantly improved with SEMA compared to controls.
  • Myocardial fibrosis was also significantly reduced with SEMA treatment.

Structured PICO

Does semaglutide improve myocardial perfusion, strain, and ectopic lipid accumulation in a mouse model of cardiometabolic heart disease?

P
Population
Obese mice fed a high-fat, high-sucrose diet to model cardiometabolic heart disease.
I
Intervention
Semaglutide
C
Comparator
Pair-fed controls (to account for reduced dietary intake)
O
Outcome
Epicardial adipose tissue volume and composition, myocardial fat fraction, adenosine myocardial perfusion reserve, systolic strain, and diastolic function (assessed by cardiovascular magnetic resonance), and myocardial fibrosis (assessed by histology)surrogate

Semaglutide reverses key imaging and histological features of obesity-induced cardiometabolic heart disease in mice, independent of weight loss from reduced caloric intake.

Cite This Study

Skacel et al. (2026) studied Obesity-induced cardiometabolic heart disease. Semaglutide vs. Pair-fed controls was evaluated on Epicardial adipose tissue volume and composition, myocardial fat fraction, adenosine myocardial perfusion reserve, systolic strain, diastolic function, and myocardial fibrosis. Semaglutide reversed ectopic lipid accumulation, impaired myocardial perfusion reserve, and diastolic dysfunction in a mouse model of cardiometabolic heart disease.

synapsesocial.com/papers/69fc2ce88b49bacb8b3481a1https://doi.org/10.1016/j.jacbts.2026.101554
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Also Consider

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  1. 1Female Mice are Protected against High-Fat Diet Induced Metabolic Syndrome and Increase the Regulatory T Cell Population in Adipose Tissue2012 · 546 citations
  2. 2Selective mobilization of adipose tissue fatty acids during energy depletion in the rat.1996 · 117 citations
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