REVIEW article
Front. Cardiovasc. Med.
Sec. Cardiac Rhythmology
Research on Epicardial Adipose Tissue as AF's Metabolic Therapeutic Target: Focus on GLP-1 Receptor Agonists
ling liu
Junlin Lu
Chongqing Rongchang Hospital of Traditional Chinese Medicine, chongqing, China
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Abstract
Epicardial adipose tissue (EAT), a metabolically active visceral fat depot anatomically contiguous with the myocardium, emerges as a critical mediator and promising metabolic therapeutic target in atrial fibrillation (AF), particularly in the context of obesity and diabetes mellitus. Pathological EAT expansion and dysfunction promote AF through paracrine and vasocrine secretion of pro-inflammatory and pro-fibrotic cytokines, extracellular vesicles (EVs) carrying arrhythmogenic cargo, direct infiltration, and modulation of local electrophysiology and autonomic signaling, thereby creating a substrate for atrial cardiomyopathy, fibrosis, electrical remodeling, and AF initiation/persistence. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), beyond their glucoregulatory and weight-loss benefits, exhibit potential cardioprotective effects relevant to AF. Crucially, GLP-1 receptors (GLP-1R) are expressed within human EAT and atria. Preclinical and clinical studies suggest that GLP-1RAs may reduce EAT volume/thickness, potentially exceeding overall weight loss, attenuate EAT inflammation and fibrosis, improve cardiomyocyte calcium handling, mitigate oxidative stress, and suppress pulmonary vein ectopy, thereby potentially reducing AF susceptibility and recurrence post-ablation. While evidence from genetic studies, meta-analyses, and specific Cardiovascular Outcomes Trials (CVOTs) supports an association between certain GLP-1RAs and reduced AF risk, conflicting data exist regarding drug-specific effects, underscoring the need for further mechanistic and outcome research. Targeting EAT modulation via GLP-1RAs represents a compelling strategy to disrupt the obesity-diabetes-AF axis, although challenges remain in elucidating precise molecular mechanisms, standardizing EAT assessment, understanding response heterogeneity, and defining the clinical role of specific GLP-1RAs within AF management algorithms(Figure 1).
Summary
Keywords
Atrial Fibrillation 1, Atrial Remodeling 5, Epicardial Adipose Tissue 2, Glucagon-Like Peptide-1 ReceptorAgonist3, therapeutic target 4
Received
18 September 2025
Accepted
19 January 2026
Copyright
© 2026 liu and Lu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Junlin Lu
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